JP2017141272A - 官能化核酸の合成のための方法 - Google Patents
官能化核酸の合成のための方法 Download PDFInfo
- Publication number
- JP2017141272A JP2017141272A JP2017074528A JP2017074528A JP2017141272A JP 2017141272 A JP2017141272 A JP 2017141272A JP 2017074528 A JP2017074528 A JP 2017074528A JP 2017074528 A JP2017074528 A JP 2017074528A JP 2017141272 A JP2017141272 A JP 2017141272A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- alkyl
- aryl
- alkenyl
- alkynyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 140
- 102000039446 nucleic acids Human genes 0.000 title claims description 70
- 108020004707 nucleic acids Proteins 0.000 title claims description 70
- 150000007523 nucleic acids Chemical class 0.000 title claims description 70
- 230000015572 biosynthetic process Effects 0.000 title abstract description 24
- 238000003786 synthesis reaction Methods 0.000 title abstract description 24
- 230000008569 process Effects 0.000 claims abstract description 71
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 54
- GWIKYPMLNBTJHR-UHFFFAOYSA-M thiosulfonate group Chemical group S(=S)(=O)[O-] GWIKYPMLNBTJHR-UHFFFAOYSA-M 0.000 claims abstract description 24
- YIKQLNRXIWIZFA-UHFFFAOYSA-N silyl dihydrogen phosphate Chemical compound OP(O)(=O)O[SiH3] YIKQLNRXIWIZFA-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 109
- 230000000903 blocking effect Effects 0.000 claims description 94
- 125000000304 alkynyl group Chemical group 0.000 claims description 89
- 125000003342 alkenyl group Chemical group 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 239000001257 hydrogen Substances 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 75
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 125000005647 linker group Chemical group 0.000 claims description 48
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 42
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 40
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 40
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 38
- 239000007787 solid Substances 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 229910052717 sulfur Inorganic materials 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 229940104302 cytosine Drugs 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 229940113082 thymine Drugs 0.000 claims description 20
- 229940035893 uracil Drugs 0.000 claims description 20
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 19
- 229930024421 Adenine Natural products 0.000 claims description 19
- 229960000643 adenine Drugs 0.000 claims description 19
- 125000002252 acyl group Chemical group 0.000 claims description 18
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 150000001768 cations Chemical class 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 10
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 2
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 183
- -1 heterocyclo Chemical group 0.000 description 97
- 238000005481 NMR spectroscopy Methods 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 125000004432 carbon atom Chemical group C* 0.000 description 57
- 235000000346 sugar Nutrition 0.000 description 47
- 239000000243 solution Substances 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 229910019142 PO4 Inorganic materials 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- 239000010452 phosphate Substances 0.000 description 29
- 125000005842 heteroatom Chemical group 0.000 description 28
- XCOBLONWWXQEBS-KPKJPENVSA-N N,O-bis(trimethylsilyl)trifluoroacetamide Chemical compound C[Si](C)(C)O\C(C(F)(F)F)=N\[Si](C)(C)C XCOBLONWWXQEBS-KPKJPENVSA-N 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 26
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 26
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 26
- 239000002777 nucleoside Substances 0.000 description 24
- 125000006239 protecting group Chemical group 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- 125000003729 nucleotide group Chemical group 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 150000008163 sugars Chemical class 0.000 description 22
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 239000002773 nucleotide Substances 0.000 description 20
- 150000003833 nucleoside derivatives Chemical class 0.000 description 19
- 230000020477 pH reduction Effects 0.000 description 19
- 239000002253 acid Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 17
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 15
- 108091034117 Oligonucleotide Proteins 0.000 description 15
- 125000004429 atom Chemical group 0.000 description 15
- 239000011669 selenium Substances 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- CMXKINNDZCNCEI-UHFFFAOYSA-N 2,2,3,3,4,4,4-heptafluoro-n-methyl-n-trimethylsilylbutanamide Chemical compound C[Si](C)(C)N(C)C(=O)C(F)(F)C(F)(F)C(F)(F)F CMXKINNDZCNCEI-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- MSPCIZMDDUQPGJ-UHFFFAOYSA-N N-methyl-N-(trimethylsilyl)trifluoroacetamide Chemical compound C[Si](C)(C)N(C)C(=O)C(F)(F)F MSPCIZMDDUQPGJ-UHFFFAOYSA-N 0.000 description 12
- YKFRUJSEPGHZFJ-UHFFFAOYSA-N N-trimethylsilylimidazole Chemical compound C[Si](C)(C)N1C=CN=C1 YKFRUJSEPGHZFJ-UHFFFAOYSA-N 0.000 description 12
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 12
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 12
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 229940125797 compound 12 Drugs 0.000 description 11
- 229940125898 compound 5 Drugs 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 239000007790 solid phase Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 125000000524 functional group Chemical group 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 8
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 8
- 230000000670 limiting effect Effects 0.000 description 8
- 238000001668 nucleic acid synthesis Methods 0.000 description 8
- 229910052698 phosphorus Inorganic materials 0.000 description 8
- 125000006413 ring segment Chemical group 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000012038 nucleophile Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- MASDFXZJIDNRTR-UHFFFAOYSA-N 1,3-bis(trimethylsilyl)urea Chemical compound C[Si](C)(C)NC(=O)N[Si](C)(C)C MASDFXZJIDNRTR-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- QRKUHYFDBWGLHJ-UHFFFAOYSA-N N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide Chemical compound FC(F)(F)C(=O)N(C)[Si](C)(C)C(C)(C)C QRKUHYFDBWGLHJ-UHFFFAOYSA-N 0.000 description 6
- HIMXYMYMHUAZLW-UHFFFAOYSA-N [[[dimethyl(phenyl)silyl]amino]-dimethylsilyl]benzene Chemical group C=1C=CC=CC=1[Si](C)(C)N[Si](C)(C)C1=CC=CC=C1 HIMXYMYMHUAZLW-UHFFFAOYSA-N 0.000 description 6
- YFONAHAKNVIHPT-UHFFFAOYSA-N [methyl-[[methyl(diphenyl)silyl]amino]-phenylsilyl]benzene Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C)N[Si](C)(C=1C=CC=CC=1)C1=CC=CC=C1 YFONAHAKNVIHPT-UHFFFAOYSA-N 0.000 description 6
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 6
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 6
- PQRFRTCWNCVQHI-UHFFFAOYSA-N chloro-dimethyl-(2,3,4,5,6-pentafluorophenyl)silane Chemical compound C[Si](C)(Cl)C1=C(F)C(F)=C(F)C(F)=C1F PQRFRTCWNCVQHI-UHFFFAOYSA-N 0.000 description 6
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- ZSMNRKGGHXLZEC-UHFFFAOYSA-N n,n-bis(trimethylsilyl)methanamine Chemical compound C[Si](C)(C)N(C)[Si](C)(C)C ZSMNRKGGHXLZEC-UHFFFAOYSA-N 0.000 description 6
- QULMGWCCKILBTO-UHFFFAOYSA-N n-[dimethylamino(dimethyl)silyl]-n-methylmethanamine Chemical compound CN(C)[Si](C)(C)N(C)C QULMGWCCKILBTO-UHFFFAOYSA-N 0.000 description 6
- QHUOBLDKFGCVCG-UHFFFAOYSA-N n-methyl-n-trimethylsilylacetamide Chemical compound CC(=O)N(C)[Si](C)(C)C QHUOBLDKFGCVCG-UHFFFAOYSA-N 0.000 description 6
- KAHVZNKZQFSBFW-UHFFFAOYSA-N n-methyl-n-trimethylsilylmethanamine Chemical compound CN(C)[Si](C)(C)C KAHVZNKZQFSBFW-UHFFFAOYSA-N 0.000 description 6
- 125000004437 phosphorous atom Chemical group 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical group CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 6
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 6
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 6
- DGIJAZGPLFOQJE-UHFFFAOYSA-N trimethylsilyl n-trimethylsilylcarbamate Chemical compound C[Si](C)(C)NC(=O)O[Si](C)(C)C DGIJAZGPLFOQJE-UHFFFAOYSA-N 0.000 description 6
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 5
- 0 B[C@@]1O[C@@](C*)C(C)C1* Chemical compound B[C@@]1O[C@@](C*)C(C)C1* 0.000 description 5
- BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 5
- 239000002841 Lewis acid Substances 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 239000004793 Polystyrene Substances 0.000 description 5
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 229940126543 compound 14 Drugs 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 5
- 239000011574 phosphorus Substances 0.000 description 5
- 229920002223 polystyrene Polymers 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 5
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 4
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 4
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 4
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 4
- 108091093094 Glycol nucleic acid Proteins 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 4
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 4
- 125000002723 alicyclic group Chemical group 0.000 description 4
- 125000004450 alkenylene group Chemical group 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 125000004103 aminoalkyl group Chemical group 0.000 description 4
- 125000000732 arylene group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000012069 chiral reagent Substances 0.000 description 4
- 229940127204 compound 29 Drugs 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 229940125877 compound 31 Drugs 0.000 description 4
- 229940127573 compound 38 Drugs 0.000 description 4
- 229960005215 dichloroacetic acid Drugs 0.000 description 4
- 125000005549 heteroarylene group Chemical group 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- 125000003835 nucleoside group Chemical group 0.000 description 4
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000005373 porous glass Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 4
- 239000010703 silicon Substances 0.000 description 4
- JFTZUZWJGUCSTE-UHFFFAOYSA-M sodium;methyl-oxido-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound [Na+].CS([O-])(=O)=S JFTZUZWJGUCSTE-UHFFFAOYSA-M 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 229910052718 tin Inorganic materials 0.000 description 4
- 239000011135 tin Substances 0.000 description 4
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 3
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 3
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 3
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 3
- YZVWMFBVTTUSAW-UHFFFAOYSA-N 2-morpholin-4-ylethanethiol Chemical compound SCCN1CCOCC1 YZVWMFBVTTUSAW-UHFFFAOYSA-N 0.000 description 3
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 3
- 108090001008 Avidin Chemical group 0.000 description 3
- IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 3
- 239000007848 Bronsted acid Substances 0.000 description 3
- UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 3
- 229940126639 Compound 33 Drugs 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 3
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 3
- XYONNSVDNIRXKZ-UHFFFAOYSA-N S-methyl methanethiosulfonate Chemical compound CSS(C)(=O)=O XYONNSVDNIRXKZ-UHFFFAOYSA-N 0.000 description 3
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 3
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 229940126086 compound 21 Drugs 0.000 description 3
- 229940126208 compound 22 Drugs 0.000 description 3
- 229940125833 compound 23 Drugs 0.000 description 3
- 229940125961 compound 24 Drugs 0.000 description 3
- 229940125846 compound 25 Drugs 0.000 description 3
- 229940125851 compound 27 Drugs 0.000 description 3
- 229940125878 compound 36 Drugs 0.000 description 3
- 229940125807 compound 37 Drugs 0.000 description 3
- 229940126540 compound 41 Drugs 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229920000620 organic polymer Polymers 0.000 description 3
- 150000004032 porphyrins Chemical class 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 229910052711 selenium Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- ORTVZLZNOYNASJ-UPHRSURJSA-N (z)-but-2-ene-1,4-diol Chemical compound OC\C=C/CO ORTVZLZNOYNASJ-UPHRSURJSA-N 0.000 description 2
- SXUXMRMBWZCMEN-UHFFFAOYSA-N 2'-O-methyl uridine Natural products COC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 2
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 2
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108020004394 Complementary RNA Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 2
- 230000037429 base substitution Effects 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940125936 compound 42 Drugs 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 125000000262 haloalkenyl group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000000232 haloalkynyl group Chemical group 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- FHBSGPWHCCIQPG-UHFFFAOYSA-N hydroxy-methyl-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound CS(S)(=O)=O FHBSGPWHCCIQPG-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229920000592 inorganic polymer Polymers 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- UYEUUXMDVNYCAM-UHFFFAOYSA-N lumazine Chemical compound N1=CC=NC2=NC(O)=NC(O)=C21 UYEUUXMDVNYCAM-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- IHCHOVVAJBADAH-UHFFFAOYSA-N n-[2-hydroxy-4-(1h-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2h-chromene-3-carboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1C(=O)NC(C(=C1)O)=CC=C1C=1C=NNC=1 IHCHOVVAJBADAH-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 125000003431 oxalo group Chemical group 0.000 description 2
- 150000002972 pentoses Chemical class 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical compound OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 2
- 235000021286 stilbenes Nutrition 0.000 description 2
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical group CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- RVCNQQGZJWVLIP-VPCXQMTMSA-N uridin-5-yloxyacetic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(OCC(O)=O)=C1 RVCNQQGZJWVLIP-VPCXQMTMSA-N 0.000 description 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- CCSBNBKMACZDGN-UHFFFAOYSA-N (2-phenoxyacetyl) 2-phenoxyacetate Chemical compound C=1C=CC=CC=1OCC(=O)OC(=O)COC1=CC=CC=C1 CCSBNBKMACZDGN-UHFFFAOYSA-N 0.000 description 1
- JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical compound C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- GFYLSDSUCHVORB-IOSLPCCCSA-N 1-methyladenosine Chemical compound C1=NC=2C(=N)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O GFYLSDSUCHVORB-IOSLPCCCSA-N 0.000 description 1
- UTAIYTHAJQNQDW-KQYNXXCUSA-N 1-methylguanosine Chemical compound C1=NC=2C(=O)N(C)C(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UTAIYTHAJQNQDW-KQYNXXCUSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 1
- RFCQJGFZUQFYRF-UHFFFAOYSA-N 2'-O-Methylcytidine Natural products COC1C(O)C(CO)OC1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-UHFFFAOYSA-N 0.000 description 1
- OVYNGSFVYRPRCG-UHFFFAOYSA-N 2'-O-Methylguanosine Natural products COC1C(O)C(CO)OC1N1C(NC(N)=NC2=O)=C2N=C1 OVYNGSFVYRPRCG-UHFFFAOYSA-N 0.000 description 1
- RFCQJGFZUQFYRF-ZOQUXTDFSA-N 2'-O-methylcytidine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-ZOQUXTDFSA-N 0.000 description 1
- OVYNGSFVYRPRCG-KQYNXXCUSA-N 2'-O-methylguanosine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=C(N)NC2=O)=C2N=C1 OVYNGSFVYRPRCG-KQYNXXCUSA-N 0.000 description 1
- WGNUTGFETAXDTJ-OOJXKGFFSA-N 2'-O-methylpseudouridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O WGNUTGFETAXDTJ-OOJXKGFFSA-N 0.000 description 1
- SXUXMRMBWZCMEN-ZOQUXTDFSA-N 2'-O-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-ZOQUXTDFSA-N 0.000 description 1
- KXSFECAJUBPPFE-UHFFFAOYSA-N 2,2':5',2''-terthiophene Chemical compound C1=CSC(C=2SC(=CC=2)C=2SC=CC=2)=C1 KXSFECAJUBPPFE-UHFFFAOYSA-N 0.000 description 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
- IQZWKGWOBPJWMX-UHFFFAOYSA-N 2-Methyladenosine Natural products C12=NC(C)=NC(N)=C2N=CN1C1OC(CO)C(O)C1O IQZWKGWOBPJWMX-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- IQZWKGWOBPJWMX-IOSLPCCCSA-N 2-methyladenosine Chemical compound C12=NC(C)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O IQZWKGWOBPJWMX-IOSLPCCCSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- AGPKHLPHPSLRED-UHFFFAOYSA-N 2-methylsulfonylsulfanylethanol Chemical compound CS(=O)(=O)SCCO AGPKHLPHPSLRED-UHFFFAOYSA-N 0.000 description 1
- VZQXUWKZDSEQRR-SDBHATRESA-N 2-methylthio-N(6)-(Delta(2)-isopentenyl)adenosine Chemical compound C12=NC(SC)=NC(NCC=C(C)C)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VZQXUWKZDSEQRR-SDBHATRESA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- RHFUOMFWUGWKKO-XVFCMESISA-N 2-thiocytidine Chemical compound S=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RHFUOMFWUGWKKO-XVFCMESISA-N 0.000 description 1
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- RDPUKVRQKWBSPK-UHFFFAOYSA-N 3-Methylcytidine Natural products O=C1N(C)C(=N)C=CN1C1C(O)C(O)C(CO)O1 RDPUKVRQKWBSPK-UHFFFAOYSA-N 0.000 description 1
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 1
- RDPUKVRQKWBSPK-ZOQUXTDFSA-N 3-methylcytidine Chemical compound O=C1N(C)C(=N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RDPUKVRQKWBSPK-ZOQUXTDFSA-N 0.000 description 1
- LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical group [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 1
- APRZHQXAAWPYHS-UHFFFAOYSA-N 4-[5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-1,3-thiazol-2-yl)tetrazol-3-ium-2-yl]benzenesulfonate Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=C(OCC(O)=O)C=CC=2)=NN1C1=CC=C(S([O-])(=O)=O)C=C1 APRZHQXAAWPYHS-UHFFFAOYSA-N 0.000 description 1
- BCZUPRDAAVVBSO-MJXNYTJMSA-N 4-acetylcytidine Chemical compound C1=CC(C(=O)C)(N)NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 BCZUPRDAAVVBSO-MJXNYTJMSA-N 0.000 description 1
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 1
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 1
- MFEFTTYGMZOIKO-UHFFFAOYSA-N 5-azacytosine Chemical compound NC1=NC=NC(=O)N1 MFEFTTYGMZOIKO-UHFFFAOYSA-N 0.000 description 1
- VKLFQTYNHLDMDP-PNHWDRBUSA-N 5-carboxymethylaminomethyl-2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C(CNCC(O)=O)=C1 VKLFQTYNHLDMDP-PNHWDRBUSA-N 0.000 description 1
- RJUNHHFZFRMZQQ-FDDDBJFASA-N 5-methoxyaminomethyl-2-thiouridine Chemical compound S=C1NC(=O)C(CNOC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RJUNHHFZFRMZQQ-FDDDBJFASA-N 0.000 description 1
- YIZYCHKPHCPKHZ-PNHWDRBUSA-N 5-methoxycarbonylmethyluridine Chemical compound O=C1NC(=O)C(CC(=O)OC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 YIZYCHKPHCPKHZ-PNHWDRBUSA-N 0.000 description 1
- ZXIATBNUWJBBGT-JXOAFFINSA-N 5-methoxyuridine Chemical compound O=C1NC(=O)C(OC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZXIATBNUWJBBGT-JXOAFFINSA-N 0.000 description 1
- SNNBPMAXGYBMHM-JXOAFFINSA-N 5-methyl-2-thiouridine Chemical compound S=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SNNBPMAXGYBMHM-JXOAFFINSA-N 0.000 description 1
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VKKXEIQIGGPMHT-UHFFFAOYSA-N 7h-purine-2,8-diamine Chemical compound NC1=NC=C2NC(N)=NC2=N1 VKKXEIQIGGPMHT-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LHSNCTVZSHGRJR-QNXMXSBRSA-N C(C)(=O)O.C(C)(=O)O.C(C)(=O)O.C(C)(=O)O.S[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO Chemical compound C(C)(=O)O.C(C)(=O)O.C(C)(=O)O.C(C)(=O)O.S[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO LHSNCTVZSHGRJR-QNXMXSBRSA-N 0.000 description 1
- 229930182476 C-glycoside Natural products 0.000 description 1
- 150000000700 C-glycosides Chemical class 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- IVDFNFBTDBNZMA-UHFFFAOYSA-N CCC[N](C)(C)CCS Chemical compound CCC[N](C)(C)CCS IVDFNFBTDBNZMA-UHFFFAOYSA-N 0.000 description 1
- WVRJSUNJYOSTAR-UHFFFAOYSA-N CCc1ccc(C)cc1CS Chemical compound CCc1ccc(C)cc1CS WVRJSUNJYOSTAR-UHFFFAOYSA-N 0.000 description 1
- HIRRKMHVXDVMGL-UHFFFAOYSA-N CCc1ccccc1CCS Chemical compound CCc1ccccc1CCS HIRRKMHVXDVMGL-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- 125000003423 D-mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 101100170604 Mus musculus Dmap1 gene Proteins 0.000 description 1
- 101100206458 Mus musculus Them4 gene Proteins 0.000 description 1
- RSPURTUNRHNVGF-IOSLPCCCSA-N N(2),N(2)-dimethylguanosine Chemical compound C1=NC=2C(=O)NC(N(C)C)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RSPURTUNRHNVGF-IOSLPCCCSA-N 0.000 description 1
- SLEHROROQDYRAW-KQYNXXCUSA-N N(2)-methylguanosine Chemical compound C1=NC=2C(=O)NC(NC)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O SLEHROROQDYRAW-KQYNXXCUSA-N 0.000 description 1
- USVMJSALORZVDV-SDBHATRESA-N N(6)-(Delta(2)-isopentenyl)adenosine Chemical compound C1=NC=2C(NCC=C(C)C)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O USVMJSALORZVDV-SDBHATRESA-N 0.000 description 1
- VQAYFKKCNSOZKM-IOSLPCCCSA-N N(6)-methyladenosine Chemical compound C1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VQAYFKKCNSOZKM-IOSLPCCCSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091005461 Nucleic proteins Chemical class 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229930185560 Pseudouridine Natural products 0.000 description 1
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 150000001241 acetals Chemical group 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 1
- 125000005841 biaryl group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000027832 depurination Effects 0.000 description 1
- 238000006642 detritylation reaction Methods 0.000 description 1
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- ZPTBLXKRQACLCR-XVFCMESISA-N dihydrouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)CC1 ZPTBLXKRQACLCR-XVFCMESISA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 1
- MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-UHFFFAOYSA-N hexopyranose Chemical group OCC1OC(O)C(O)C(O)C1O WQZGKKKJIJFFOK-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical class O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- WZRYXYRWFAPPBJ-PNHWDRBUSA-N methyl uridin-5-yloxyacetate Chemical compound O=C1NC(=O)C(OCC(=O)OC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 WZRYXYRWFAPPBJ-PNHWDRBUSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003551 oxepanyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- RUUFMHUAHUPZSS-UHFFFAOYSA-N oxido-oxo-sulfinophosphanium Chemical class P(=O)(=O)S(=O)O RUUFMHUAHUPZSS-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- PUXKSJCSTXMIKR-UHFFFAOYSA-N phenyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CC=CC=C1 PUXKSJCSTXMIKR-UHFFFAOYSA-N 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005597 polymer membrane Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- RUDNWZFWWJFUSF-UHFFFAOYSA-M potassium;(4-methylphenyl)-oxido-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound [K+].CC1=CC=C(S([O-])(=O)=S)C=C1 RUDNWZFWWJFUSF-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000005495 pyridazyl group Chemical group 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
- 125000006853 reporter group Chemical group 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 description 1
- RHFUOMFWUGWKKO-UHFFFAOYSA-N s2C Natural products S=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 RHFUOMFWUGWKKO-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000001583 thiepanyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- XCOBLONWWXQEBS-UHFFFAOYSA-N trimethylsilyl 2,2,2-trifluoro-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(C(F)(F)F)=N[Si](C)(C)C XCOBLONWWXQEBS-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- YIZYCHKPHCPKHZ-UHFFFAOYSA-N uridine-5-acetic acid methyl ester Natural products COC(=O)Cc1cn(C2OC(CO)C(O)C2O)c(=O)[nH]c1=O YIZYCHKPHCPKHZ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
i)構造IaのH−ホスホネートをシリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)シリルオキシホスホネートを構造IIaのチオスルホネート試薬と反応させて、構造IIIaのホスホロチオトリエステルをもたらすステップと、を含み、
構造IaのH−ホスホネートは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IIaのチオスルホネート試薬は、次の構造:
式中、
Xは、アルキル、シクロアルキル、またはヘテロアリールであり、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
構造IIIaのホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200である、プロセスを提供する。
1,1,3,3−テトラメチル−1,3−ジフェニルジシラザン、
1,3−ジメチル−1,1,3,3−テトラフェニルジシラザン、
1−(トリメチルシリル)イミダゾール、
N−トリメチルシリル−N−メチルトリフルオロアセトアミド、
ビス(ジメチルアミノ)ジメチルシラン、
ブロモトリメチルシラン、
クロロジメチル(ペンタフルオロフェニル)シラン、
クロロトリエチルシラン、
クロロトリイソプロピルシラン、
クロロトリメチルシラン、
ジクロロジメチルシラン、
ヘキサメチルジシラザン、
N,N′−ビス(トリメチルシリル)尿素、
N,N−ビス(トリメチルシリル)メチルアミン、
N,N−ジメチルトリメチルシリルアミン、
N,O−ビス(トリメチルシリル)アセトアミド、
N,O−ビス(トリメチルシリル)カルバメート、
N,O−ビス(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−トリメチルシリルアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
N−tert−ブチルジメチルシリル−N−メチルトリフルオロアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
トリメチルシリルトリフラート、
トリエチルシリルトリフラート、
トリイソプロピルシリルトリフラート、または
tert−ブチルジメチルシリルトリフラートから選択される、プロセスを提供する。
i)構造Ibの非立体無作為性リン酸連結を含むH−ホスホネートを、シリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)シリルオキシホスホネートを、構造IIbのチオスルホネート試薬と反応させて、構造IIIbの非立体無作為性リン酸連結を含むホスホロチオトリエステルをもたらすステップと、を含み、
構造Ibの非立体無作為性リン酸連結を含むH−ホスホネートは、次の構造:
式中、
Wは、独立して、O、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IIbのチオスルホネート試薬は、次の構造:
式中、
Xは、アルキル、シクロアルキル、アリール、またはヘテロアリールであり、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
構造IIIbの非立体無作為性リン酸連結を含むキラルホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、NH、またはCH2から選択され、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200である、プロセスを提供する。
1,1,3,3−テトラメチル−1,3−ジフェニルジシラザン、
1,3−ジメチル−1,1,3,3−テトラフェニルジシラザン、
1−(トリメチルシリル)イミダゾール、
N−トリメチルシリル−N−メチルトリフルオロアセトアミド、
ビス(ジメチルアミノ)ジメチルシラン、
ブロモトリメチルシラン、
クロロジメチル(ペンタフルオロフェニル)シラン、
クロロトリエチルシラン、
クロロトリイソプロピルシラン、
クロロトリメチルシラン、
ジクロロジメチルシラン、
ヘキサメチルジシラザン、
N,N′−ビス(トリメチルシリル)尿素、
N,N−ビス(トリメチルシリル)メチルアミン、
N,N−ジメチルトリメチルシリルアミン、
N,O−ビス(トリメチルシリル)アセトアミド、
N,O−ビス(トリメチルシリル)カルバメート、
N,O−ビス(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−トリメチルシリルアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
N−tert−ブチルジメチルシリル−N−メチルトリフルオロアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
トリメチルシリルトリフラート、
トリエチルシリルトリフラート、
トリイソプロピルシリルトリフラート、または
tert−ブチルジメチルシリルトリフラートから選択される、プロセスを提供する。
i)構造IcのH−ホスホネートを、シリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)シリルオキシホスホネートを、構造IVcのビス(チオスルホネート)試薬と反応させて、構造Vcのチオスルホネート基を含むホスホロチオトリエステルをもたらすステップと、
iii)構造Vcのチオスルホネート基を含むホスホロチオトリエステルを、構造VIcの求核試薬と反応させて、構造IIIcのホスホロチオトリエステルをもたらすステップと、を含み、
構造IcのH−ホスホネートは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IVcのビス(チオスルホネート)試薬は、次の構造:
式中、
Xは、アルキレン、アルケニレン、アリーレン、またはヘテロアリーレンであり、
各R6は、独立して、アルキル、シクロアルキル、アリール、またはヘテロアリールであり、
構造VIcの求核試薬は、次の構造:
R7−SHを有し、式中、R7は、アルキル、アルケニル、アリール、ヘテロシクロ、アミノアルキル、または(ヘテロシクロ)アルキルから選択され、
構造IIIcのホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
Rは、R7−S−S−X−であり、
R7は、アルキル、アルケニル、アリール、ヘテロシクロ、アミノアルキル、または(ヘテロシクロ)アルキルであり、
Xは、アルキレン、アルケニレン、アリーレン、またはヘテロアリーレンであり、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IcのH−ホスホネートのリン酸連結は、ホスホロチオトリエステルが構造Vcのチオスルホネート基を含み、構造IIIcのホスホロチオトリエステルが、任意で、非立体無作為性リン酸連結を含んでもよい、プロセスを提供する。
1,1,3,3−テトラメチル−1,3−ジフェニルジシラザン、
1,3−ジメチル−1,1,3,3−テトラフェニルジシラザン、
1−(トリメチルシリル)イミダゾール、
N−トリメチルシリル−N−メチルトリフルオロアセトアミド、
ビス(ジメチルアミノ)ジメチルシラン、
ブロモトリメチルシラン、
クロロジメチル(ペンタフルオロフェニル)シラン、
クロロトリエチルシラン、
クロロトリイソプロピルシラン、
クロロトリメチルシラン、
ジクロロジメチルシラン、
ヘキサメチルジシラザン、
N,N′−ビス(トリメチルシリル)尿素、
N,N−ビス(トリメチルシリル)メチルアミン、
N,N−ジメチルトリメチルシリルアミン、
N,O−ビス(トリメチルシリル)アセトアミド、
N,O−ビス(トリメチルシリル)カルバメート、
N,O−ビス(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−トリメチルシリルアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
N−tert−ブチルジメチルシリル−N−メチルトリフルオロアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
トリメチルシリルトリフラート、
トリエチルシリルトリフラート、
トリイソプロピルシリルトリフラート、または
tert−ブチルジメチルシリルトリフラートから選択される、プロセスを提供する。
参照による組み込み
特定の化学用語
一実施形態において、「シクロアルキル」は、置換される。別段の指定がない限り、「シクロアルキル」は、非置換である。
一実施形態において、「ヘテロアリール」は、置換される。別段の指定がない限り、「ヘテロアリール」は、非置換である。
特定の核酸に関する用語
新規な官能化核酸および核酸プロドラッグの調製のための合成方法
i)構造IaのH−ホスホネートをシリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)シリルオキシホスホネートを構造IIaのチオスルホネート試薬と反応させて、構造IIIaのホスホロチオトリエステルをもたらすステップと、を含み、
構造IaのH−ホスホネートは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IIaのチオスルホネート試薬は、次の構造:
式中、
Xは、アルキル、シクロアルキル、またはヘテロアリールであり、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
構造IIIaのホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200である、プロセスを提供する。
1,1,3,3−テトラメチル−1,3−ジフェニルジシラザン、
1,3−ジメチル−1,1,3,3−テトラフェニルジシラザン、
1−(トリメチルシリル)イミダゾール、
N−トリメチルシリル−N−メチルトリフルオロアセトアミド、
ビス(ジメチルアミノ)ジメチルシラン、
ブロモトリメチルシラン、
クロロジメチル(ペンタフルオロフェニル)シラン、
クロロトリエチルシラン、
クロロトリイソプロピルシラン、
クロロトリメチルシラン、
ジクロロジメチルシラン、
ヘキサメチルジシラザン、
N,N′−ビス(トリメチルシリル)尿素、
N,N−ビス(トリメチルシリル)メチルアミン、
N,N−ジメチルトリメチルシリルアミン、
N,O−ビス(トリメチルシリル)アセトアミド、
N,O−ビス(トリメチルシリル)カルバメート、
N,O−ビス(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−トリメチルシリルアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
N−tert−ブチルジメチルシリル−N−メチルトリフルオロアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
トリメチルシリルトリフラート、
トリエチルシリルトリフラート、
トリイソプロピルシリルトリフラート、または
tert−ブチルジメチルシリルトリフラートから選択される、プロセスを提供する。
i)構造Ibの非立体無作為性リン酸連結を含むH−ホスホネートを、シリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)シリルオキシホスホネートを、構造IIbのチオスルホネート試薬と反応させて、構造IIIbの非立体無作為性リン酸連結を含むホスホロチオトリエステルをもたらすステップと、を含み、
構造Ibの非立体無作為性リン酸連結を含むH−ホスホネートは、次の構造:
式中、
Wは、独立して、O、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IIbのチオスルホネート試薬は、次の構造:
式中、
Xは、アルキル、シクロアルキル、アリール、またはヘテロアリールであり、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
構造IIIbの非立体無作為性リン酸連結を含むキラルホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、NH、またはCH2から選択され、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200である、プロセスを提供する。
1,1,3,3−テトラメチル−1,3−ジフェニルジシラザン、
1,3−ジメチル−1,1,3,3−テトラフェニルジシラザン、
1−(トリメチルシリル)イミダゾール、
N−トリメチルシリル−N−メチルトリフルオロアセトアミド、
ビス(ジメチルアミノ)ジメチルシラン、
ブロモトリメチルシラン、
クロロジメチル(ペンタフルオロフェニル)シラン、
クロロトリエチルシラン、
クロロトリイソプロピルシラン、
クロロトリメチルシラン、
ジクロロジメチルシラン、
ヘキサメチルジシラザン、
N,N′−ビス(トリメチルシリル)尿素、
N,N−ビス(トリメチルシリル)メチルアミン、
N,N−ジメチルトリメチルシリルアミン、
N,O−ビス(トリメチルシリル)アセトアミド、
N,O−ビス(トリメチルシリル)カルバメート、
N,O−ビス(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−トリメチルシリルアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
N−tert−ブチルジメチルシリル−N−メチルトリフルオロアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
トリメチルシリルトリフラート、
トリエチルシリルトリフラート、
トリイソプロピルシリルトリフラート、または
tert−ブチルジメチルシリルトリフラートから選択される、プロセスを提供する。
i)構造IcのH−ホスホネートを、シリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)シリルオキシホスホネートを、構造IVcのビス(チオスルホネート)試薬と反応させて、構造Vcのチオスルホネート基を含むホスホロチオトリエステルをもたらすステップと、
iii)構造Vcのチオスルホネート基を含むホスホロチオトリエステルを、構造VIcの求核試薬と反応させて、構造IIIcのホスホロチオトリエステルをもたらすステップと、を含み、
構造IcのH−ホスホネートは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、`
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IVcのビス(チオスルホネート)試薬は、次の構造:
式中、
Xは、アルキレン、アルケニレン、アリーレン、またはヘテロアリーレンであり、
各R6は、独立して、アルキル、シクロアルキル、アリール、またはヘテロアリールであり、
構造VIcの求核試薬は、次の構造:
R7−SHを有し、式中、R7は、アルキル、アルケニル、アリール、ヘテロシクロ、アミノアルキル、または(ヘテロシクロ)アルキルから選択され、
構造IIIcのホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
Rは、R7−S−S−X−であり、
R7は、アルキル、アルケニル、アリール、ヘテロシクロ、アミノアルキル、または(ヘテロシクロ)アルキルであり、
Xは、アルキレン、アルケニレン、アリーレン、またはヘテロアリーレンであり、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IcのH−ホスホネートのリン酸連結は、ホスホロチオトリエステルが構造Vcのチオスルホネート基を含み、構造IIIcのホスホロチオトリエステルが、任意で、非立体無作為性リン酸連結を含んでもよい、プロセスを提供する。
1,1,3,3−テトラメチル−1,3−ジフェニルジシラザン、
1,3−ジメチル−1,1,3,3−テトラフェニルジシラザン、
1−(トリメチルシリル)イミダゾール、
N−トリメチルシリル−N−メチルトリフルオロアセトアミド、
ビス(ジメチルアミノ)ジメチルシラン、
ブロモトリメチルシラン、
クロロジメチル(ペンタフルオロフェニル)シラン、
クロロトリエチルシラン、
クロロトリイソプロピルシラン、
クロロトリメチルシラン、
ジクロロジメチルシラン、
ヘキサメチルジシラザン、
N,N′−ビス(トリメチルシリル)尿素、
N,N−ビス(トリメチルシリル)メチルアミン、
N,N−ジメチルトリメチルシリルアミン、
N,O−ビス(トリメチルシリル)アセトアミド、
N,O−ビス(トリメチルシリル)カルバメート、
N,O−ビス(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−(トリメチルシリル)トリフルオロアセトアミド、
N−メチル−N−トリメチルシリルアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
N−tert−ブチルジメチルシリル−N−メチルトリフルオロアセトアミド、
N−メチル−N−トリメチルシリルヘプタフルオロブチルアミド、
トリメチルシリルトリフラート、
トリエチルシリルトリフラート、
トリイソプロピルシリルトリフラート、または
tert−ブチルジメチルシリルトリフラートから選択される、プロセスを提供する。
修飾オリゴヌクレオチド
本発明の方法に使用される反応条件および試薬。
条件
固体支持体上での合成
連結部分
合成のための溶媒
ブロッキング基を除去するための酸性化条件
ブロッキング部分または基の除去
オリゴヌクレオシドホスホロチオエート連結の立体化学
核酸塩基および修飾核酸塩基
ヌクレオチド/ヌクレオシドの修飾糖
ブロッキング基
実施例
実施例1−メタンチオスルホネート試薬の合成
1H NMR(399MHz,CDCl3)δ4.86(s,2H),3.45(s,6H);13C NMR(100MHz,CDCl3)δ52.15,41.50。
1H NMR(399MHz,CDCl3)δ3.55(s,4H),3.40(s,6H);13C NMR(100MHz,CDCl3)δ50.67,35.96。
TMS開裂が完了した後、溶媒を真空下で除去し、残渣をDCM中に再溶解し、その溶液を水で洗浄し、乾燥させ(MgSO4)、濾過し、真空で濃縮する。
粗製アルコールをピリジン(5ml)中に再溶解し、TsCl(0.55mmol)を添加する。室温で18時間後、溶媒を除去し、残渣をDCM中に再溶解し、その溶液を水で洗浄し、乾燥させ(MgSO4)、濾過し、真空で濃縮する。カラムクロマトグラフィーによる精製によって、純粋な化合物37を得る。
実施例3−ビス(メタンチオスルホネート)試薬を使用した、ホスホロチオトリエステルの代替的合成
実施例4−H−固相でホスホロチオトリエステルをもたらすためのホスホネートのチオアルキル化
実施例5−溶液相でホスホロチオトリエステルをもたらすためのH−ホスホネートのチオアルキル化
実施例6−H−ホスホネートの立体選択的チオアルキル化
Claims (1)
- 構造IIIaのホスホロチオトリエステルの調製のためのプロセスであって、
i)構造IaのH−ホスホネートをシリル化試薬と反応させて、シリルオキシホスホネートをもたらすステップと、
ii)前記シリルオキシホスホネートを構造IIaのチオスルホネート試薬と反応させて、構造IIIaのホスホロチオトリエステルをもたらすステップと、を含み、
構造Iaの前記H−ホスホネートは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200であり、
構造IIaの前記チオスルホネート試薬は、次の構造:
Xは、アルキル、シクロアルキル、またはヘテロアリールであり、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
構造IIIaの前記ホスホロチオトリエステルは、次の構造:
式中、
Wは、独立して、O、S、NH、またはCH2から選択され、
Rは、アルキル、アルケニル、アルキニル、シクロアルキル、アリール、アラルキル、ヘテロアリール、ヘテロアラルキル、またはR1−R2であり、
R1は、−S−アルケニレン−、−S−アルキレン−、−S−アルキレン−アリール−アルキレン−、−S−CO−アリール−アルキレン−、または−S−CO−アルキレン−アリール−アルキレン−から選択され、
R2は、ヘテロシクロ−アルキレン−S−、ヘテロシクロ−アルケニレン−S−、アミノアルキル−S−、または(アルキル)4N−アルキレン−S−から選択され、
R3は、−OH、−SH、−NRdRd、−N3、ハロゲン、水素、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−P(O)(Re)2、−HP(O)(Re)、−ORa、または−SRcであり、
Y1は、O、NRd、S、またはSeであり、
Raは、ブロッキング基であり、
Rcは、ブロッキング基であり、
各場合のRdは、独立して、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
各場合のReは、独立して、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、もしくはヘテロアリール−Y2−、またはNa+1、Li+1、もしくはK+1であるカチオンであり、
Y2は、O、NRd、またはSであり、
各場合のR4は、独立して、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRcであり、Rbは、ブロッキング基であり、
各場合のBaは、独立して、ブロックまたは非ブロックのアデニン、シトシン、グアニン、チミン、ウラシル、または修飾核酸塩基であり、
R5は、水素、ブロッキング基、固体支持体に結合した連結部分、または核酸に結合した連結部分であり、
nは、1〜約200である、プロセス。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161509526P | 2011-07-19 | 2011-07-19 | |
US61/509,526 | 2011-07-19 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014521681A Division JP6128529B2 (ja) | 2011-07-19 | 2012-07-13 | 官能化核酸の合成のための方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017141272A true JP2017141272A (ja) | 2017-08-17 |
JP6490133B2 JP6490133B2 (ja) | 2019-03-27 |
Family
ID=47558410
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014521681A Active JP6128529B2 (ja) | 2011-07-19 | 2012-07-13 | 官能化核酸の合成のための方法 |
JP2017074528A Active JP6490133B2 (ja) | 2011-07-19 | 2017-04-04 | 官能化核酸の合成のための方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014521681A Active JP6128529B2 (ja) | 2011-07-19 | 2012-07-13 | 官能化核酸の合成のための方法 |
Country Status (16)
Country | Link |
---|---|
US (3) | US9605019B2 (ja) |
EP (2) | EP2734208B1 (ja) |
JP (2) | JP6128529B2 (ja) |
KR (1) | KR20140068884A (ja) |
CN (2) | CN103796657B (ja) |
AU (1) | AU2012284265B2 (ja) |
BR (1) | BR112014001244A2 (ja) |
CA (1) | CA2842358C (ja) |
DK (1) | DK2734208T3 (ja) |
ES (1) | ES2626488T3 (ja) |
HK (1) | HK1198479A1 (ja) |
IL (1) | IL230522B (ja) |
MX (1) | MX347361B (ja) |
RU (1) | RU2014105311A (ja) |
SG (1) | SG10201700554VA (ja) |
WO (1) | WO2013012758A1 (ja) |
Families Citing this family (70)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
KR101141544B1 (ko) | 2009-03-13 | 2012-05-03 | 한국과학기술원 | 에스아이알엔에이 다중 접합체 및 이의 제조방법 |
AU2010270714B2 (en) | 2009-07-06 | 2015-08-13 | Wave Life Sciences Ltd. | Novel nucleic acid prodrugs and methods use thereof |
US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
DK2734208T3 (en) | 2011-07-19 | 2017-06-19 | Wave Life Sciences Ltd | PROCEDURES FOR SYNTHESIS OF FUNCTIONALIZED NUCLEIC ACIDS |
SG11201500232UA (en) | 2012-07-13 | 2015-04-29 | Wave Life Sciences Pte Ltd | Chiral control |
JP6246121B2 (ja) | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | キラル核酸アジュバント |
US9598458B2 (en) | 2012-07-13 | 2017-03-21 | Wave Life Sciences Japan, Inc. | Asymmetric auxiliary group |
US20160257961A1 (en) * | 2013-11-06 | 2016-09-08 | Solstice Biologics, Ltd. | Polynucleotide constructs having disulfide groups |
JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
US10160969B2 (en) | 2014-01-16 | 2018-12-25 | Wave Life Sciences Ltd. | Chiral design |
WO2015125845A1 (ja) * | 2014-02-20 | 2015-08-27 | 塩野義製薬株式会社 | 含窒素非芳香族複素環を含む核酸のリン酸部位修飾 |
GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
EP3183346A4 (en) | 2014-08-22 | 2018-10-24 | Auckland Uniservices Limited | Channel modulators |
RU2708237C2 (ru) | 2014-08-22 | 2019-12-05 | Общество с ограниченной ответственностью "НооГен" | Модифицированные олигонуклеотиды и способ их получения |
AU2015327836B2 (en) | 2014-10-03 | 2021-07-01 | Cold Spring Harbor Laboratory | Targeted augmentation of nuclear gene output |
DK3234131T3 (da) | 2014-12-16 | 2020-06-29 | Roche Innovation Ct Copenhagen As | Fremgangsmåde til screening af kiral toksicitet |
CN108026527B (zh) * | 2015-06-15 | 2022-05-10 | Mpeg La有限责任公司 | 确定的多偶联寡核苷酸 |
EP3315507A4 (en) * | 2015-06-26 | 2019-02-27 | Kyowa Hakko Kirin Co., Ltd. | An oligonucleotide |
MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
AU2016334232B2 (en) | 2015-10-09 | 2022-05-26 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods thereof |
KR20220105174A (ko) | 2015-10-09 | 2022-07-26 | 유니버시티 오브 사우스앰톤 | 유전자 발현의 조절 및 탈조절된 단백질 발현의 스크리닝 |
ES2903394T3 (es) | 2015-12-14 | 2022-04-01 | Cold Spring Harbor Laboratory | Composiciones para el tratamiento de la retinitis pigmentosa 13 |
WO2017106382A1 (en) | 2015-12-14 | 2017-06-22 | Cold Spring Harbor Laboratory | Compositions and methods for treatment of central nervous system diseases |
US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
EP3389671A4 (en) | 2015-12-14 | 2019-07-17 | Cold Spring Harbor Laboratory | ANTISENSE OLIGOMERS FOR THE TREATMENT OF ALAGILLE'S SYNDROME |
CN109312343B (zh) | 2015-12-14 | 2022-09-27 | 冷泉港实验室 | 用于治疗常染色体显性精神发育迟滞5型和Dravet综合征的反义寡聚体 |
WO2017106283A1 (en) | 2015-12-14 | 2017-06-22 | Cold Spring Harbor Laboratory | Compositions and methods for treatment of liver diseases |
EP3431591B1 (en) * | 2016-03-09 | 2020-09-16 | Tokyo University of Science Foundation | Nucleic acid oligomer for rna hybrid formation |
AU2017234150B2 (en) | 2016-03-13 | 2021-09-16 | Wave Life Sciences Ltd. | Compositions and methods for phosphoramidite and oligonucleotide synthesis |
KR102417646B1 (ko) | 2016-03-14 | 2022-07-07 | 에프. 호프만-라 로슈 아게 | Pd-l1 발현의 감소를 위한 올리고뉴클레오티드 |
MA45469A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques de bêta-caténine et leurs utilisations |
MA45471A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques de phosphatidylinositol-3-kinase et leurs utilisations |
MA45470A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques kras et leurs utilisations |
MA45349A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques egfr et leurs utilisations |
MA45328A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Compositions acide nucléique-polypeptide et utilisations de celles-ci |
MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
JP2019520339A (ja) | 2016-06-03 | 2019-07-18 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | オリゴヌクレオチド、その組成物および方法 |
KR20190058477A (ko) | 2016-08-17 | 2019-05-29 | 솔스티스 바이올로직스, 리미티드 | 폴리뉴클레오티드 구축물 |
EP3544987A4 (en) | 2016-11-23 | 2020-11-18 | Wave Life Sciences Ltd. | COMPOSITIONS AND SYNTHESIS OF PHOSPHORAMIDITES AND OLIGONUCLEOTIDES |
CA3049424A1 (en) | 2017-01-06 | 2018-07-12 | Avidity Biosciences Llc | Nucleic acid-polypeptide compositions and methods of inducing exon skipping |
CN106667176A (zh) * | 2017-03-01 | 2017-05-17 | 戴建华 | 一种治疗痤疮的药枕 |
AU2018231832A1 (en) * | 2017-03-10 | 2019-08-08 | Quiapeg Pharmaceuticals Ab | Releasable conjugates |
TW201904587A (zh) | 2017-06-02 | 2019-02-01 | 新加坡商波濤生命科學有限公司 | 寡核苷酸組合物及其使用方法 |
JP2020522510A (ja) | 2017-06-02 | 2020-07-30 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | オリゴヌクレオチド組成物及びその使用方法 |
WO2018237194A1 (en) | 2017-06-21 | 2018-12-27 | Wave Life Sciences Ltd. | COMPOUNDS, COMPOSITIONS AND METHODS OF SYNTHESIS |
US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
GB201711809D0 (en) | 2017-07-21 | 2017-09-06 | Governors Of The Univ Of Alberta | Antisense oligonucleotide |
AU2018316159A1 (en) | 2017-08-08 | 2020-02-06 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods thereof |
RS65031B1 (sr) | 2017-08-25 | 2024-02-29 | Stoke Therapeutics Inc | Antisens oligomeri za lečenje stanja i bolesti |
EP3684755A4 (en) | 2017-09-18 | 2022-03-02 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE PREPARATION TECHNOLOGIES |
CN111655268B (zh) | 2017-10-04 | 2024-03-26 | 艾维迪提生物科学公司 | 核酸-多肽组合物及其用途 |
WO2019075357A1 (en) | 2017-10-12 | 2019-04-18 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE COMPOSITIONS AND RELATED METHODS |
EP3697910A4 (en) | 2017-10-18 | 2021-07-14 | Sarepta Therapeutics, Inc. | ANTISENSE OLIGOMERIC COMPOUNDS |
KR20200070367A (ko) | 2017-10-23 | 2020-06-17 | 스톡 테라퓨틱스, 인크. | 넌센스 매개 rna 분해 기반 병태 및 질환 치료를 위한 안티센스 올리고머 |
KR20240007965A (ko) | 2017-12-06 | 2024-01-17 | 어비디티 바이오사이언시스 인크. | 근위축증 및 근긴장성 이영양증을 치료하는 조성물 및 방법 |
EP3849660A1 (en) | 2018-09-12 | 2021-07-21 | QuiaPEG Pharmaceuticals AB | Releasable glp-1 conjugates |
KR102270138B1 (ko) * | 2018-09-17 | 2021-06-28 | 삼성에스디아이 주식회사 | 실리카 막 형성용 조성물, 실리카 막의 제조방법 및 실리카 막 |
KR102630499B1 (ko) | 2018-12-21 | 2024-01-30 | 어비디티 바이오사이언시스 인크. | 항트랜스페린 수용체 항체 및 이의 용도 |
JP2022535588A (ja) | 2019-06-06 | 2022-08-09 | アビディティー バイオサイエンシーズ,インク. | 核酸ポリペプチド組成物およびその使用 |
CN114375297A (zh) | 2019-06-06 | 2022-04-19 | 艾维迪提生物科学公司 | Una亚酰胺及其用途 |
EP4121063A4 (en) | 2020-03-19 | 2024-07-03 | Avidity Biosciences Inc | COMPOSITIONS AND METHODS FOR TREATING FACIO-SCAPULO-HUMERAL MUSCULAR DYSTROPHY |
KR20220161378A (ko) | 2020-03-27 | 2022-12-06 | 어비디티 바이오사이언시스 인크. | 근이영양증의 치료용 조성물 및 방법 |
WO2021231107A1 (en) | 2020-05-11 | 2021-11-18 | Stoke Therapeutics, Inc. | Opa1 antisense oligomers for treatment of conditions and diseases |
JP2023526533A (ja) | 2020-05-22 | 2023-06-21 | ウェイブ ライフ サイエンシズ リミテッド | 二本鎖オリゴヌクレオチド組成物及びそれに関連する方法 |
AU2022266383A1 (en) * | 2021-04-28 | 2023-11-16 | Japan Science And Technology Agency | Artificial nucleic acid and nucleic acid delivering method using same |
WO2023043953A1 (en) | 2021-09-16 | 2023-03-23 | Avidity Biosciences, Inc. | Compositions and methods of treating facioscapulohumeral muscular dystrophy |
WO2023220737A2 (en) * | 2022-05-13 | 2023-11-16 | Adarx Pharmaceuticals, Inc. | Oligonucleotides having a synthetic backbone and synthesis thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3484473A (en) * | 1967-05-12 | 1969-12-16 | Buckman Labor Inc | Methylene bisesters of thiolsulfonic acids |
JP2002533087A (ja) * | 1998-12-21 | 2002-10-08 | ジェネンカー インターナショナル,インコーポレイティド | 複数荷電変種を有する化学修飾酵素 |
WO2011005761A1 (en) * | 2009-07-06 | 2011-01-13 | Ontorii, Inc | Novel nucleic acid prodrugs and methods use thereof |
Family Cites Families (686)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2878264A (en) | 1959-03-17 | Substituted amino alcohols | ||
DE1144279B (de) | 1957-09-26 | 1963-02-28 | Robins Co Inc A H | Verfahren zur Herstellung von 3-Aryl-3-hydroxypyrrolidinen und deren Salzen |
US3135766A (en) | 1961-10-03 | 1964-06-02 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
DE1934150A1 (de) | 1968-07-10 | 1970-01-15 | Pennwalt Corp | Neue 1-Alkanoyloxy-1,2,4,5-tetrahydro-3H,3-benzazepine |
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US3745162A (en) | 1970-08-31 | 1973-07-10 | Robins Co Inc A H | 1,2,3,4-tetrahydroisoquinoline-2-(thio)-carboxamides |
GB1448437A (en) | 1973-02-24 | 1976-09-08 | Beecham Group Ltd | Diphenylpropylamines |
US4022791A (en) | 1975-06-03 | 1977-05-10 | Pfizer Inc. | 2-Aminomethyl-3,4-dihydronaphthalenes |
GB1504424A (en) | 1975-08-09 | 1978-03-22 | Beecham Group Ltd | Isoquinoline-derived aminoethers |
BR7807288A (pt) | 1977-11-08 | 1979-06-12 | Genentech Inc | Processo para sintese de polinucleotidos |
DD133885B1 (de) | 1978-01-04 | 1981-02-25 | Hans Lehmann | Mittel zur bekaempfung von phytopathogenen bakterien und pilzen |
US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
US4668777A (en) | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
US4542142A (en) | 1982-11-22 | 1985-09-17 | Roussel Uclaf | Insecticidal cyclopropane carboxylic acid derivatives with 3-unsaturated-side chain |
DE3329892A1 (de) | 1983-08-18 | 1985-03-07 | Köster, Hubert, Prof. Dr., 2000 Hamburg | Verfahren zur herstellung von oligonucleotiden |
USRE34069E (en) | 1983-08-18 | 1992-09-15 | Biosyntech Gmbh | Process for the preparation of oligonucleotides |
US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
US5643889A (en) | 1984-07-11 | 1997-07-01 | Temple University-Of The Commonwealth System Of Pennsylvania | Cholesterol conjugates of 2'5'-oligoadenylate derivatives and antiviral uses thereof |
FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
FR2576898B1 (fr) | 1985-02-01 | 1988-01-08 | Lafon Labor | Derives de 3-phenyl-tetrahydropyridine, procede de preparation et utilisation en therapeutique |
US4659774A (en) | 1985-11-01 | 1987-04-21 | American Hoechst Corporation | Support for solid-phase oligonucleotide synthesis |
US4840956A (en) | 1986-02-18 | 1989-06-20 | Warner-Lambert Company | Novel disubstituted-7-pyrrolidinoquinoline antibacterial agents |
US4735949A (en) | 1986-02-18 | 1988-04-05 | Warner-Lambert Company | Disubstituted-7-pyrrolidinonaphthyridine antibacterial agents |
IL83663A0 (en) | 1986-10-27 | 1988-01-31 | Robins Co Inc A H | Preparation of 3-pyrrolidinols |
AU598946B2 (en) | 1987-06-24 | 1990-07-05 | Howard Florey Institute Of Experimental Physiology And Medicine | Nucleoside derivatives |
DE3884517T2 (de) | 1987-07-30 | 1994-02-10 | Kupat Holim Health Insurance | Biologisch aktive Carbonsäureester. |
US4923901A (en) | 1987-09-04 | 1990-05-08 | Millipore Corporation | Membranes with bound oligonucleotides and peptides |
US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
US4945158A (en) | 1988-08-12 | 1990-07-31 | American Cyanamid Company | Antidiabetic phosphonates |
US4943629A (en) | 1988-08-12 | 1990-07-24 | American Cyanamid Company | Antidiabetic alpha-substituted phosphonates |
US5262530A (en) | 1988-12-21 | 1993-11-16 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
US5047524A (en) | 1988-12-21 | 1991-09-10 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
JP2794461B2 (ja) | 1989-08-17 | 1998-09-03 | 有機合成薬品工業株式会社 | ホスホアミダイト化合物及びそれを用いたオリゴリボヌクレオチドの固相合成法 |
US5141813A (en) | 1989-08-28 | 1992-08-25 | Clontech Laboratories, Inc. | Multifunctional controlled pore glass reagent for solid phase oligonucleotide synthesis |
US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
CA2029273A1 (en) | 1989-12-04 | 1991-06-05 | Christine L. Brakel | Modified nucleotide compounds |
US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
CA2071897A1 (en) | 1989-12-28 | 1991-06-29 | Richard A. Glennon | Sigma receptor ligands and the use thereof |
AU651569B2 (en) | 1990-01-11 | 1994-07-28 | Isis Pharmaceuticals, Inc. | Compositions and methods for detecting and modulating RNA activity and gene expression |
US5620963A (en) | 1991-10-15 | 1997-04-15 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating protein kinase C having phosphorothioate linkages of high chiral purity |
US6339066B1 (en) | 1990-01-11 | 2002-01-15 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate βI, βII, γ, δ, Ε, ζ and η isoforms of human protein kinase C |
US5852188A (en) | 1990-01-11 | 1998-12-22 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US7101993B1 (en) | 1990-01-11 | 2006-09-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides containing 2′-O-modified purines |
US5635488A (en) | 1991-10-15 | 1997-06-03 | Isis Pharmaceuticals, Inc. | Compounds having phosphorodithioate linkages of high chiral purity |
US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
US5506212A (en) | 1990-01-11 | 1996-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides with substantially chirally pure phosphorothioate linkages |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5212295A (en) | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
US5914396A (en) | 1990-01-11 | 1999-06-22 | Isis Pharmaceuticals, Inc. | 2'-O-modified nucleosides and phosphoramidites |
US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US5151510A (en) | 1990-04-20 | 1992-09-29 | Applied Biosystems, Inc. | Method of synethesizing sulfurized oligonucleotide analogs |
US5292875A (en) | 1990-04-20 | 1994-03-08 | Lynx Therapeutics, Inc. | Method of synthesizing sulfurized oligonucleotide analogs |
BR9106486A (pt) | 1990-05-23 | 1993-05-25 | Isis Pharmaceuticals Inc | Composicao para modulacao da atividade de um rna e processo para tratamento de um organismo que tem uma doenca que se caracteriza para producao indesejada de uma proteina |
US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
WO1994022886A1 (en) | 1993-03-30 | 1994-10-13 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US6121433A (en) | 1990-07-27 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having nitrogen-containing linkages |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
US5783682A (en) | 1990-07-27 | 1998-07-21 | Isis Pharmaceuticals, Inc. | Oligonucleotide mimics having nitrogen-containing linkages |
US5792844A (en) | 1990-07-27 | 1998-08-11 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent nitrogen atoms |
US6087482A (en) | 1990-07-27 | 2000-07-11 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
US5834607A (en) | 1990-07-27 | 1998-11-10 | Isis Pharmaceuticals, Inc. | Amines and methods of making and using the same |
US5223618A (en) | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
BR9106702A (pt) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals Inc | Analogo de oligonucleotideos e processos para modular a producao de uma proteina por um organismo e para tratar um organismo |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
US5998603A (en) | 1994-09-29 | 1999-12-07 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analogs, and oligomers thereof |
US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
JPH04348044A (ja) | 1991-02-21 | 1992-12-03 | Matsushita Electron Corp | 半導体用樹脂封止装置 |
US5512668A (en) | 1991-03-06 | 1996-04-30 | Polish Academy Of Sciences | Solid phase oligonucleotide synthesis using phospholane intermediates |
US20020183502A1 (en) | 1991-05-21 | 2002-12-05 | Mesmaeker Alain De | Backbone-modified oligonucleotide analogs and methods for using same |
US7015315B1 (en) | 1991-12-24 | 2006-03-21 | Isis Pharmaceuticals, Inc. | Gapped oligonucleotides |
US6414112B1 (en) | 1991-05-24 | 2002-07-02 | Ole Buchardt | Peptide nucleic acids having 2,6-diaminopurine nucleobases |
JPH04348077A (ja) | 1991-05-24 | 1992-12-03 | Nec Corp | 薄膜トランジスタ |
WO1992022655A1 (en) | 1991-06-10 | 1992-12-23 | Lucky Limited | Hepatitis c diagnostics and vaccines |
US5359052A (en) | 1991-08-05 | 1994-10-25 | Polish Academy Of Sciences | Chalcophospholanes useful in the synthesis of oligonucleoside phosphorothioates, phosphorodithioates and related selenates |
US5646267A (en) | 1991-08-05 | 1997-07-08 | Polish Academy Of Sciences | Method of making oligonucleotides and oligonucleotide analogs using phospholanes and enantiomerically resolved phospholane analogues |
US7119184B2 (en) | 1991-08-12 | 2006-10-10 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
US6369209B1 (en) | 1999-05-03 | 2002-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
US5576302A (en) | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
EP0655088B1 (en) | 1991-10-15 | 2002-07-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
US5654284A (en) | 1991-10-15 | 1997-08-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating RAF kinase having phosphorothioate linkages of high chiral purity |
US5599797A (en) | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5661134A (en) | 1991-10-15 | 1997-08-26 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity |
US5607923A (en) | 1991-10-15 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity |
ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
US6235887B1 (en) | 1991-11-26 | 2001-05-22 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines |
US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
ATE515510T1 (de) | 1991-12-24 | 2011-07-15 | Isis Pharmaceuticals Inc | Durch dna-abschnitte unterbrochene modifizierte oligonukleotide |
GB9213601D0 (en) | 1992-06-26 | 1992-08-12 | Mastico Robert A | Protein based delivery system |
US7067497B2 (en) | 1992-09-29 | 2006-06-27 | Isis Pharmaceuticals, Inc. | Modulation of telomere length by oligonucleotides having a G-core sequence |
US6444656B1 (en) | 1992-12-23 | 2002-09-03 | Biochem Pharma, Inc. | Antiviral phosphonate nucleotides |
US6005107A (en) | 1992-12-23 | 1999-12-21 | Biochem Pharma, Inc. | Antiviral compounds |
ES2086997T3 (es) | 1993-01-25 | 1996-07-01 | Hybridon Inc | Oligonucleotido-alquilfosfonatos y -alquilfosfonotioatos. |
CA2159632A1 (en) | 1993-03-31 | 1994-10-13 | Ashis Kumar Saha | Novel 5'-substituted nucleosides and oligomers produced therefrom |
WO1994022888A1 (en) | 1993-03-31 | 1994-10-13 | Sterlingwinthrop Inc. | Bifunctional nucleosides, oligomers thereof, and methods of making and using the same |
US5955591A (en) | 1993-05-12 | 1999-09-21 | Imbach; Jean-Louis | Phosphotriester oligonucleotides, amidites and method of preparation |
US6015886A (en) | 1993-05-24 | 2000-01-18 | Chemgenes Corporation | Oligonucleotide phosphate esters |
DE69412704T2 (de) | 1993-06-10 | 1999-02-04 | Idemitsu Petrochemical Co | Spritzgiessform |
US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
US5643989A (en) | 1993-10-29 | 1997-07-01 | Azdel, Inc. | Fiber reinforced functionalized polyolefin composites |
US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
DE4435728A1 (de) | 1994-01-19 | 1995-07-20 | Boehringer Mannheim Gmbh | Biotinsilan-Verbindungen und diese Verbindungen enthaltende Bindematrix |
US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
ATE222604T1 (de) | 1994-02-22 | 2002-09-15 | Novozymes As | Methode zur herstellung einer variante eines lipolytischen enzymes |
US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
US5871966A (en) | 1994-05-11 | 1999-02-16 | Novo Nordisk A/S | Enzyme with endo-1,3(4)-β- Glucanase activity |
US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
EP0685475B1 (en) | 1994-05-31 | 1999-01-13 | Bayer Ag | Amino-benzofuryl-and thienyl-derivatives |
HRP950288A2 (en) | 1994-05-31 | 1997-08-31 | Bayer Ag | Oxalylamino-benzofuran- and benzothienyl-derivatives |
US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
WO1996002555A1 (en) | 1994-07-15 | 1996-02-01 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
AU3675195A (en) | 1994-09-07 | 1996-03-27 | Hybridon, Inc. | Oligonucleotide prodrugs |
US5681940A (en) | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
EP0807171A1 (en) | 1994-12-22 | 1997-11-19 | HYBRIDON, Inc. | Synthesis of stereospecific oligonucleotide phosphorothioates |
GB9501465D0 (en) * | 1995-01-25 | 1995-03-15 | King S College London | Nucleoside phosphorothioate derivatives,synthesis and use thereof |
US6222025B1 (en) | 1995-03-06 | 2001-04-24 | Isis Pharmaceuticals, Inc. | Process for the synthesis of 2′-O-substituted pyrimidines and oligomeric compounds therefrom |
US6166197A (en) | 1995-03-06 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions |
EP0739983B1 (en) | 1995-04-27 | 2009-12-30 | Takara Bio Inc. | Gene encoding lacto-n-biosidase |
US6004813A (en) | 1995-05-11 | 1999-12-21 | Applied Research Systems Ars Holding N.V. | Il-6 activity inhibitor |
AU5855296A (en) | 1995-05-19 | 1996-11-29 | Glycomed Incorporated | Collection of activated glycoside compounds and their biolog ical use |
AU5871196A (en) | 1995-05-23 | 1996-12-24 | Hybridon, Inc. | Methods and compounds for the synthesis of oligonucleotides and the oligonucleotides thereby produced |
ATE194990T1 (de) | 1995-05-23 | 2000-08-15 | Hybridon Inc | Synthon für stereoselektive oligonukleotid- synthese |
EP0831854A4 (en) | 1995-06-06 | 2001-01-24 | Isis Pharmaceuticals Inc | OLIGONUCLEOTIDS WITH PHOSPHOROTHIOATE BINDINGS OF HIGH CHIRAL PURITY |
US5932450A (en) | 1995-06-07 | 1999-08-03 | Gen-Probe Incorporated | Enzymatic synthesis of oligonucleotides using digestible templates |
US5795765A (en) | 1995-06-29 | 1998-08-18 | Takara Shuzo Co., Ltd. | Gene encoding endoglycoceramidase |
US5824503A (en) | 1995-06-29 | 1998-10-20 | Takara Shuzo Co, Ltd. | Gene encoding endoglycoceramidase activator |
US6017700A (en) | 1995-08-04 | 2000-01-25 | Bayer Corporation | Cationic oligonucleotides, and related methods of synthesis and use |
US5936080A (en) | 1996-05-24 | 1999-08-10 | Genta Incorporated | Compositions and methods for the synthesis of organophosphorus derivatives |
WO1997009443A1 (en) | 1995-09-05 | 1997-03-13 | Michigan State University | PROCESS FOR THE ISOLATION AND PURIFICATION OF TAXOL AND TAXANES FROM TAXUS spp |
US6476216B1 (en) | 1995-10-20 | 2002-11-05 | Mcgill University | Preparation of phosphorothioate oligomers |
US6160109A (en) | 1995-10-20 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Preparation of phosphorothioate and boranophosphate oligomers |
US5734041A (en) | 1995-10-20 | 1998-03-31 | Mcgill University | Preparation of chiral phosphorothioate oligomers |
US7018793B1 (en) | 1995-12-07 | 2006-03-28 | Diversa Corporation | Combinatorial screening of mixed populations of organisms |
US6214805B1 (en) | 1996-02-15 | 2001-04-10 | The United States Of America As Represented By The Department Of Health And Human Services | RNase L activators and antisense oligonucleotides effective to treat RSV infections |
CA2246503A1 (en) | 1996-02-15 | 1997-08-21 | National Institutes Of Health | Rnase l activators and antisense oligonucleotides effective to treat rsv infections |
GB9604669D0 (en) | 1996-03-05 | 1996-05-01 | Ciba Geigy Ag | Chemical compounds |
US5824669A (en) | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
DK0898618T3 (da) | 1996-05-10 | 2008-02-25 | Novozymes As | Fremgangsmåde til tilvejebringelse af hidtil ukendte DNA-sekvenser |
US5856465A (en) | 1996-05-24 | 1999-01-05 | Polska Akademia Nauk Centrum Badan Molekularnych I Makromolekularnych | Compositions and methods for the synthesis of chirally pure organophosphorus nucleoside derivatives |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
DE19622783A1 (de) | 1996-06-07 | 1997-12-11 | Hoechst Ag | Isolierung der Biosynthesegene für Pseudo-Oligosaccharide aus Streptomyces glaucescens GLA.O und ihre Verwendung |
AU726821B2 (en) | 1996-07-16 | 2000-11-23 | Gen-Probe Incorporated | Methods for detecting and amplifying nucleic acid sequences using modified oligonucleotides having increased target specific Tm |
DE69734783T2 (de) | 1996-07-24 | 2006-08-17 | Buchardt, Dorte | Peptidnukleinsäuren mit erhöhter bindungsaffinität, sequenzspezifität und löslichkeit |
WO1998007734A1 (en) | 1996-08-21 | 1998-02-26 | Hybridon, Inc. | Oligonucleotide prodrugs |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
GB9621522D0 (en) | 1996-10-16 | 1996-12-04 | Biocompatibles Ltd | Synthesis of phosphorus compounds |
US6172209B1 (en) | 1997-02-14 | 2001-01-09 | Isis Pharmaceuticals Inc. | Aminooxy-modified oligonucleotides and methods for making same |
US6639062B2 (en) | 1997-02-14 | 2003-10-28 | Isis Pharmaceuticals, Inc. | Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom |
US6369237B1 (en) | 1997-03-07 | 2002-04-09 | President And Fellows Of Harvard College | DNA glycosylase inhibitors, and uses related thereto |
US6015887A (en) | 1997-04-11 | 2000-01-18 | Isis Pharmaceuticals, Inc. | Chiral peptide nucleic acids and methods for preparing same |
US6468983B2 (en) | 1997-04-21 | 2002-10-22 | The Cleveland Clinic Foundation | RNase L activators and antisense oligonucleotides effective to treat telomerase-expressing malignancies |
PL184612B1 (pl) | 1997-04-25 | 2002-11-29 | Pan | Sposób wytwarzania modyfikowanych P chiralnych analogów nukleotydów |
JP2001501975A (ja) | 1997-05-28 | 2001-02-13 | ペーター・エー・ニールセン | 亢進した細胞取り込みを有する結合ペプチド核酸 |
EP0991635A1 (en) | 1997-06-27 | 2000-04-12 | The Procter & Gamble Company | Pro-fragrance cyclic acetals |
AU8512598A (en) | 1997-07-25 | 1999-02-16 | Hybridon, Inc. | Oligonuclotides having 3' terminal stereospecific phosphorothioates |
GB9717158D0 (en) | 1997-08-13 | 1997-10-22 | King S College London | Solution synthesis of oligonucleotides and their phosphorothioate analogues |
US6767739B2 (en) | 2001-07-30 | 2004-07-27 | Isis Pharmaceuticals Inc. | Antisense modulation of microsomal triglyceride transfer protein expression |
US6383808B1 (en) | 2000-09-11 | 2002-05-07 | Isis Pharmaceuticals, Inc. | Antisense inhibition of clusterin expression |
US6750344B1 (en) | 1997-09-05 | 2004-06-15 | Isis Pharmaceuticals, Inc. | Amine compounds and combinatorial libraries comprising same |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
DE19741715A1 (de) | 1997-09-22 | 1999-03-25 | Hoechst Ag | Pentopyranosyl-Nucleosid, seine Herstellung und Verwendung |
US6232463B1 (en) | 1997-10-09 | 2001-05-15 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US6617438B1 (en) | 1997-11-05 | 2003-09-09 | Sirna Therapeutics, Inc. | Oligoribonucleotides with enzymatic activity |
US6528640B1 (en) | 1997-11-05 | 2003-03-04 | Ribozyme Pharmaceuticals, Incorporated | Synthetic ribonucleic acids with RNAse activity |
US6080543A (en) | 1997-12-08 | 2000-06-27 | E. & J. Gallo Winery | Detection of fungal pathogens |
US6582936B1 (en) | 1997-12-12 | 2003-06-24 | The Regents Of The University Of California | Methods for making nucleic acids |
US6248519B1 (en) | 1998-03-11 | 2001-06-19 | E & J Gallo Winery | Detection of fermentation-related microorganisms |
US7045610B2 (en) | 1998-04-03 | 2006-05-16 | Epoch Biosciences, Inc. | Modified oligonucleotides for mismatch discrimination |
AU3884199A (en) | 1998-05-06 | 1999-11-23 | Ottawa Health Research Institute | Methods for the prevention and treatment of parasitic infections and related diseases using cpg oligonucleotides |
JP2002514397A (ja) | 1998-05-14 | 2002-05-21 | コーリー ファーマシューティカル ゲーエムベーハー | CpGオリゴヌクレオチドを用いる造血調節の方法 |
US6867294B1 (en) | 1998-07-14 | 2005-03-15 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
US6242589B1 (en) | 1998-07-14 | 2001-06-05 | Isis Pharmaceuticals, Inc. | Phosphorothioate oligonucleotides having modified internucleoside linkages |
AU764532B2 (en) | 1998-07-27 | 2003-08-21 | University Of Iowa Research Foundation, The | Stereoisomers of CpG oligonucleotides and related methods |
DE69929444T2 (de) | 1998-08-10 | 2006-09-28 | Antigenics Inc., Woburn | Cpg-zusammensetzungen, saponin-adjuvantien und verfahren zu deren verwendung |
WO2000023444A1 (en) | 1998-10-21 | 2000-04-27 | Abbott Laboratories | 5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds |
US6995259B1 (en) | 1998-10-23 | 2006-02-07 | Sirna Therapeutics, Inc. | Method for the chemical synthesis of oligonucleotides |
AU1742600A (en) | 1998-11-25 | 2000-06-13 | Isis Pharmaceuticals, Inc. | Identification of disease predictive nucleic acids |
US6451524B1 (en) | 1998-11-25 | 2002-09-17 | Isis Pharmaceuticals, Inc. | Identification of disease predictive nucleic acids |
CA2702148C (en) | 1999-01-06 | 2014-03-04 | Genenews Inc. | Method of profiling gene expression in a human subject having an infectious disease |
US6265172B1 (en) | 1999-02-08 | 2001-07-24 | University Of Kentucky | Diagnostic test and therapy for manganese superoxide dismutate (mNsod) associated diseases |
US6121437A (en) | 1999-03-16 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Phosphate and thiophosphate protecting groups |
US6506594B1 (en) | 1999-03-19 | 2003-01-14 | Cornell Res Foundation Inc | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
GB9907245D0 (en) | 1999-03-29 | 1999-05-26 | Goldsborough Andrew | Cleavage of nucleic acids from solid supports |
JP3072345B1 (ja) | 1999-03-31 | 2000-07-31 | 農林水産省家畜衛生試験場長 | 豚丹毒菌の組換えサブユニットワクチン |
US5998148A (en) | 1999-04-08 | 1999-12-07 | Isis Pharmaceuticals Inc. | Antisense modulation of microtubule-associated protein 4 expression |
US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
US6300069B1 (en) | 1999-05-03 | 2001-10-09 | Qiagen Gmbh | Generation and amplification of nucleic acids from ribonucleic acids |
US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
US6066500A (en) | 1999-06-25 | 2000-05-23 | Isis Pharmaceuticals Inc. | Antisense modulation of Beta catenin expression |
US6271004B1 (en) | 1999-06-25 | 2001-08-07 | Display Systems Biotech A/S | Method for improved reverse transcription at high temperatures |
US6414135B1 (en) | 1999-07-07 | 2002-07-02 | Isis Pharmaceuticals, Inc. | C3′-methylene hydrogen phosphonate monomers and related compounds |
US20030092647A1 (en) | 2001-08-08 | 2003-05-15 | Crooke Rosanne M. | Antisense modulation of cholesteryl ester transfer protein expression |
US6147200A (en) | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
US7264932B2 (en) | 1999-09-24 | 2007-09-04 | Applera Corporation | Nuclease inhibitor cocktail |
MXPA02003108A (es) | 1999-09-25 | 2003-10-14 | Univ Iowa Res Found | Acidos nucleicos inmunoestimuladores. |
US6949520B1 (en) | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
AU783118B2 (en) | 1999-09-27 | 2005-09-29 | Coley Pharmaceutical Gmbh | Methods related to immunostimulatory nucleic acid-induced interferon |
US20020082227A1 (en) | 1999-09-30 | 2002-06-27 | Scott Henry | Use of oligonucleotides for inhibition of complement activation |
US6309836B1 (en) * | 1999-10-05 | 2001-10-30 | Marek Kwiatkowski | Compounds for protecting hydroxyls and methods for their use |
AU7863200A (en) | 1999-10-06 | 2001-05-10 | Quark Biotech, Inc. | Method for enrichment of natural antisense messenger rna |
GB9924285D0 (en) | 1999-10-14 | 1999-12-15 | Avecia Ltd | Process |
US20010055761A1 (en) | 1999-10-29 | 2001-12-27 | Agilent Technologies | Small scale dna synthesis using polymeric solid support with functionalized regions |
FR2800750B1 (fr) | 1999-11-05 | 2003-01-31 | Centre Nat Rech Scient | Proteines membranaires ctl (choline transporter like) impliquees dans le transport de la choline |
WO2001040515A1 (en) | 1999-11-12 | 2001-06-07 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
US6322985B1 (en) | 1999-12-27 | 2001-11-27 | Technion Research And Development Foundation Ltd. | Abundant, well distributed and hyperpolymorphic simple sequence repeats in prokaryote genomes and use of same for prokaryote classification and typing |
US7055094B2 (en) | 1999-12-30 | 2006-05-30 | Rutgers, The State University Of New Jersey | Virtual tags and the process of virtual tagging utilizing user feedback in transformation rules |
JP2004510953A (ja) | 1999-12-30 | 2004-04-08 | キャボット コーポレイション | 改良された性質を有するセンサー |
US6649750B1 (en) | 2000-01-05 | 2003-11-18 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotide compounds |
US6159697A (en) | 2000-01-19 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Antisense modulation of Smad7 expression |
US7585847B2 (en) | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
US6495677B1 (en) | 2000-02-15 | 2002-12-17 | Kanda S. Ramasamy | Nucleoside compounds |
US6936432B2 (en) | 2000-03-01 | 2005-08-30 | Message Pharmaceuticals | Bacterial RNase P proteins and their use in identifying antibacterial compounds |
GB0004889D0 (en) | 2000-03-01 | 2000-04-19 | Avecia Ltd | Synthesis of oligonucleotides |
AU2001245823A1 (en) | 2000-03-17 | 2001-10-03 | Corixa Corporation | Novel amphipathic aldehydes and their use as adjuvants and immunoeffectors |
JP4219590B2 (ja) | 2000-04-20 | 2009-02-04 | エフ.ホフマン−ラ ロシュ アーゲー | ピロリジン及びピペリジン誘導体並びに神経変性障害の治療のためのこれらの使用 |
DE10019756A1 (de) | 2000-04-20 | 2001-10-25 | Bayer Ag | Verfahren zur Herstellung von superabsorbierenden Polymeren aus Polyacrylnitrilen |
US20020013287A1 (en) | 2000-05-09 | 2002-01-31 | Reliable Biopharmaceuticals, Inc. St Louis Missouri | Polymeric compounds useful as prodrugs |
US6492171B2 (en) | 2000-05-16 | 2002-12-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of TERT expression |
US6815542B2 (en) | 2000-06-16 | 2004-11-09 | Ribapharm, Inc. | Nucleoside compounds and uses thereof |
EP1307469B1 (en) | 2000-08-03 | 2008-01-23 | Boehringer Mannheim Gmbh | Nucleic acid binding compounds containing pyrazolo¬3,4-d pyrimidine analogues of purin-2,6-diamine and their uses |
US6725412B1 (en) | 2000-08-15 | 2004-04-20 | Dolby Laboratories Licensing Corporation | Low latency data encoder |
US6809195B1 (en) | 2000-08-16 | 2004-10-26 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotides |
US6559279B1 (en) | 2000-09-08 | 2003-05-06 | Isis Pharmaceuticals, Inc. | Process for preparing peptide derivatized oligomeric compounds |
EP1366077B1 (en) | 2000-09-15 | 2011-05-25 | Coley Pharmaceutical GmbH | PROCESS FOR HIGH THROUGHPUT SCREENING OF CpG-BASED IMMUNO-AGONIST/ANTAGONIST |
EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
GB0024752D0 (en) | 2000-10-10 | 2000-11-22 | Univ Belfast | Oxidative halogenation of aromatic compounds |
WO2002032450A2 (en) | 2000-10-18 | 2002-04-25 | Glaxosmithkline Biologicals S.A. | Vaccines |
US6372492B1 (en) | 2000-10-30 | 2002-04-16 | Isis Pharmaceuticals, Inc. | Antisense modulation of talin expression |
US6682889B1 (en) | 2000-11-08 | 2004-01-27 | Becton, Dickinson And Company | Amplification and detection of organisms of the Chlamydiaceae family |
NL1016978C2 (nl) | 2000-12-22 | 2002-06-25 | Robert Jan Colenbrander | Inrichting en werkwijze voor het verpakken en bereiden van voedsel en werkwijze voor het vervaardigen van een dergelijke inrichting. |
CN1267446C (zh) | 2001-01-22 | 2006-08-02 | 默克公司 | 作为依赖于rna的rna病毒聚合酶的抑制剂的核苷衍生物 |
US8008459B2 (en) | 2001-01-25 | 2011-08-30 | Evolva Sa | Concatemers of differentially expressed multiple genes |
DK1356037T3 (da) | 2001-01-25 | 2011-06-27 | Evolva Ltd | Bibliotek med en samling af celler |
NZ526507A (en) | 2001-01-26 | 2005-07-29 | Commw Scient Ind Res Org | Methods and means for producing efficient silencing construct using recombinational cloning |
US20050277133A1 (en) | 2001-05-18 | 2005-12-15 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
WO2002097134A2 (en) | 2001-05-25 | 2002-12-05 | Isis Pharmaceuticals, Inc. | Modified peptide nucleic acid |
GB0113523D0 (en) | 2001-06-04 | 2001-07-25 | Torotrak Dev Ltd | An Hydraulic control circuit for a continuosly variable transmission |
US20030069410A1 (en) | 2001-06-14 | 2003-04-10 | Isis Pharmaceuticals, Inc. | Methods for preparing oligonucleotides having chiral phosphorothioate linkages |
US20050019915A1 (en) | 2001-06-21 | 2005-01-27 | Bennett C. Frank | Antisense modulation of superoxide dismutase 1, soluble expression |
CZ20033515A3 (cs) | 2001-06-29 | 2005-01-12 | Chiron Corporation | Kompozice vakcíny HCV E1E2 |
WO2003004602A2 (en) | 2001-07-03 | 2003-01-16 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
US7205399B1 (en) | 2001-07-06 | 2007-04-17 | Sirna Therapeutics, Inc. | Methods and reagents for oligonucleotide synthesis |
US6440739B1 (en) | 2001-07-17 | 2002-08-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of glioma-associated oncogene-2 expression |
US7425545B2 (en) | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
US6455308B1 (en) | 2001-08-01 | 2002-09-24 | Isis Pharmaceuticals, Inc. | Antisense modulation of serum amyloid A4 expression |
US7888324B2 (en) | 2001-08-01 | 2011-02-15 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
US7259150B2 (en) | 2001-08-07 | 2007-08-21 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein (a) expression |
WO2003020884A2 (en) | 2001-08-14 | 2003-03-13 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Method for rapid generation of mature dendritic cells |
EP1418877A2 (en) | 2001-08-24 | 2004-05-19 | Massachusetts Institute Of Technology | Reagents that facilitate the purification of compounds synthesized on a solid support |
US7049122B2 (en) | 2001-09-21 | 2006-05-23 | Academia Sinica | Mutant-type lipases and applications thereof |
US6933288B2 (en) | 2002-02-04 | 2005-08-23 | Isis Pharmaceuticals, Inc. | Pyranosyl cytosines: pharmaceutical formulations and methods |
JP4348044B2 (ja) | 2002-02-12 | 2009-10-21 | 株式会社キラルジェン | 立体規則性の高いジヌクレオシドホスホロチオエートの製造法 |
US20040149587A1 (en) | 2002-02-15 | 2004-08-05 | George Hradil | Electroplating solution containing organic acid complexing agent |
US20030159938A1 (en) | 2002-02-15 | 2003-08-28 | George Hradil | Electroplating solution containing organic acid complexing agent |
US20050096284A1 (en) | 2002-02-20 | 2005-05-05 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
US8232383B2 (en) | 2002-02-20 | 2012-07-31 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
RU2004128943A (ru) | 2002-02-28 | 2005-04-20 | Байота, Инк. (Us) | Средства, имитирующие нуклеотиды, и их пролекарственные формы |
EP1485396A2 (en) | 2002-02-28 | 2004-12-15 | Biota, Inc. | Nucleoside 5'-monophosphate mimics and their prodrugs |
US7288376B2 (en) | 2002-03-22 | 2007-10-30 | Council Of Scientific And Industrial Research | Method of detection of SP-A2 gene variants useful for prediction of predisposition to aspergillosis |
US20040102394A1 (en) | 2002-11-23 | 2004-05-27 | Isis Pharmaceuticals Inc. | Modulation of huntingtin interacting protein 2 expression |
US7247621B2 (en) | 2002-04-30 | 2007-07-24 | Valeant Research & Development | Antiviral phosphonate compounds and methods therefor |
AU2003237875A1 (en) | 2002-05-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
WO2003100017A2 (en) | 2002-05-24 | 2003-12-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having modified nucleoside units |
US20040014957A1 (en) | 2002-05-24 | 2004-01-22 | Anne Eldrup | Oligonucleotides having modified nucleoside units |
US7507808B2 (en) | 2002-12-12 | 2009-03-24 | Isis Pharmaceuticals, Inc. | Modulation of endothelial lipase expression |
AU2003248708A1 (en) | 2002-06-17 | 2003-12-31 | Isis Pharmaceuticals, Inc. | Oligomeric compounds that include carbocyclic nucleosides and their use in gene modulation |
JP4598519B2 (ja) | 2002-06-20 | 2010-12-15 | サイトス バイオテクノロジー アーゲー | アジュバントとして使用するためのパッケージ化されたウィルス様粒子:調製法及び使用法 |
WO2004003228A1 (en) | 2002-07-01 | 2004-01-08 | Unisearch Limited | Genotyping method |
EP2314690A1 (en) | 2002-07-10 | 2011-04-27 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA-interference by single-stranded RNA molecules |
US20040023905A1 (en) | 2002-07-31 | 2004-02-05 | Isis Pharmaceuticals Inc. | Antisense modulation of LAR expression |
US20080274989A1 (en) | 2002-08-05 | 2008-11-06 | University Of Iowa Research Foundation | Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof |
US20050042646A1 (en) | 2002-08-05 | 2005-02-24 | Davidson Beverly L. | RNA interference suppresion of neurodegenerative diseases and methods of use thereof |
US20050255086A1 (en) | 2002-08-05 | 2005-11-17 | Davidson Beverly L | Nucleic acid silencing of Huntington's Disease gene |
US8729036B2 (en) | 2002-08-07 | 2014-05-20 | University Of Massachusetts | Compositions for RNA interference and methods of use thereof |
AU2003259735A1 (en) | 2002-08-08 | 2004-02-25 | Sirna Therapeutics, Inc. | Small-mer compositions and methods of use |
AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
US7414116B2 (en) | 2002-08-23 | 2008-08-19 | Illumina Cambridge Limited | Labelled nucleotides |
WO2004024919A1 (en) | 2002-09-13 | 2004-03-25 | Replicor, Inc. | Non-sequence complementary antiviral oligonucleotides |
US7572604B2 (en) | 2002-10-07 | 2009-08-11 | Isis Innovation Limited | Modified carbohydrate processing enzyme |
US7030230B2 (en) | 2002-10-25 | 2006-04-18 | Isis Pharmaceuticals, Inc. | Process of purifying phosphoramidites |
MXPA05004588A (es) | 2002-10-29 | 2005-12-14 | Coley Pharmaceutical Group Ltd | Metodos y productos relacionados con el tratamiento y prevencion de infeccion de virus de hepatitis c. |
US20040147020A1 (en) | 2002-11-01 | 2004-07-29 | The Regents Of The University Of Colorado, A Body Corporate | Dopamine neurons from human embryonic stem cells |
AU2003291721A1 (en) | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | Phosphorous-linked oligomeric compounds and their use in gene modulation |
AU2003291755A1 (en) | 2002-11-05 | 2004-06-07 | Isis Pharmaceuticals, Inc. | Oligomers comprising modified bases for binding cytosine and uracil or thymine and their use |
CA2505090A1 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Conjugated oligomeric compounds and their use in gene modulation |
EP1562971B1 (en) | 2002-11-05 | 2014-02-12 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
US7381527B2 (en) | 2002-11-06 | 2008-06-03 | Council Of Scientific And Industrial Research | Method of detection of SP-A2 gene variants |
CA2505801A1 (en) | 2002-11-13 | 2004-05-27 | Rosanne Crooke | Antisense modulation of apolipoprotein b expression |
US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
EP1560931B1 (en) | 2002-11-14 | 2011-07-27 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
EP2239329A1 (en) | 2003-03-07 | 2010-10-13 | Alnylam Pharmaceuticals, Inc. | Therapeutic compositions |
AU2003225705A1 (en) | 2003-03-07 | 2004-09-30 | Ribapharm Inc. | Cytidine analogs and methods of use |
CA2524255C (en) | 2003-03-21 | 2014-02-11 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
GB0306657D0 (en) | 2003-03-24 | 2003-04-30 | Avecia Ltd | Process and compounds |
EP1606398A1 (en) | 2003-03-26 | 2005-12-21 | Cytos Biotechnology AG | Melan-a peptide analogue-virus-like-particle conjugates |
US7537767B2 (en) | 2003-03-26 | 2009-05-26 | Cytis Biotechnology Ag | Melan-A- carrier conjugates |
ITRM20030149A1 (it) | 2003-04-02 | 2004-10-03 | Giuliani Spa | Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico |
US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
US7452901B2 (en) | 2003-04-25 | 2008-11-18 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
AU2004233989A1 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
WO2004096233A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Nucleoside phosphonate conjugates |
US7407965B2 (en) | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
US7470724B2 (en) | 2003-04-25 | 2008-12-30 | Gilead Sciences, Inc. | Phosphonate compounds having immuno-modulatory activity |
US20090247488A1 (en) | 2003-04-25 | 2009-10-01 | Carina Cannizzaro | Anti-inflammatory phosphonate compounds |
WO2005002626A2 (en) | 2003-04-25 | 2005-01-13 | Gilead Sciences, Inc. | Therapeutic phosphonate compounds |
US20050261237A1 (en) | 2003-04-25 | 2005-11-24 | Boojamra Constantine G | Nucleoside phosphonate analogs |
CN101410120A (zh) | 2003-04-25 | 2009-04-15 | 吉里德科学公司 | 抗炎的膦酸酯化合物 |
CA2523083C (en) | 2003-04-25 | 2014-07-08 | Gilead Sciences, Inc. | Antiviral phosphonate analogs |
US7432261B2 (en) | 2003-04-25 | 2008-10-07 | Gilead Sciences, Inc. | Anti-inflammatory phosphonate compounds |
US7045306B2 (en) | 2003-04-28 | 2006-05-16 | The General Hospital Corporation | Method for identifying compounds in vitro that modulate the dysregulation of transcription of transcription mediated by mutant huntingtin protein |
US7214491B2 (en) | 2003-05-07 | 2007-05-08 | E. I. Du Pont De Nemours And Company | Δ-12 desaturase gene suitable for altering levels of polyunsaturated fatty acids in oleaginous yeasts |
CA2526893C (en) | 2003-05-14 | 2010-10-26 | Japan Science And Technology Agency | Inhibition of the expression of huntingtin gene |
WO2005002507A2 (en) | 2003-06-03 | 2005-01-13 | Isis Pharmaceuticals, Inc. | Modulation of survivin expression |
JP2007524615A (ja) | 2003-06-20 | 2007-08-30 | コーリー ファーマシューティカル ゲーエムベーハー | 低分子トール様レセプター(tlr)アンタゴニスト |
EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
JP2011088935A (ja) | 2003-08-08 | 2011-05-06 | Chiralgen Ltd | リン原子修飾ヌクレオチド類縁体の製造のための光学活性ヌクレオシド3’−ホスホロアミダイト |
JP2005089441A (ja) | 2003-08-08 | 2005-04-07 | Toudai Tlo Ltd | 立体規則性の高いリン原子修飾ヌクレオチド類縁体の製造法 |
US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
CA2535802A1 (en) | 2003-08-21 | 2005-03-03 | Griffith University | Novel sulfenamides |
RU2006108577A (ru) | 2003-08-21 | 2007-09-27 | Гриффит Юниверсити (Au) | Новые сульфенамиды |
CA2537114C (en) | 2003-08-27 | 2012-10-02 | Biota, Inc. | Tricyclic nucleosides or nucleotides as therapeutic agents |
ES2382807T3 (es) | 2003-08-28 | 2012-06-13 | Takeshi Imanishi | Nuevos ácidos nucleicos artificiales del tipo de enlace N-O con reticulación |
JP4580870B2 (ja) | 2003-09-02 | 2010-11-17 | 株式会社キラルジェン | リボヌクレオチド又はリボヌクレオチド誘導体の製造方法 |
JP4616175B2 (ja) | 2003-09-02 | 2011-01-19 | 株式会社キラルジェン | 5’−ホスフィチル化モノマーおよびh−ホスホネートオリゴヌクレオチド誘導体の製造方法 |
US20050053981A1 (en) | 2003-09-09 | 2005-03-10 | Swayze Eric E. | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
DK3342425T3 (da) | 2003-09-09 | 2020-03-16 | Geron Corp | Modificerede oligonukleotider til inhibering af telomerase |
US20050074801A1 (en) | 2003-09-09 | 2005-04-07 | Monia Brett P. | Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry |
US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
EP1670518B1 (en) | 2003-09-12 | 2014-05-21 | University of Massachusetts | Rna interference for the treatment of gain-of-function disorders |
WO2008005562A2 (en) | 2006-07-07 | 2008-01-10 | University Of Massachusetts | Rna silencing compositions and methods for the treatment of huntington's disease |
GB0323968D0 (en) | 2003-10-13 | 2003-11-19 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
UA88457C2 (ru) | 2003-10-30 | 2009-10-26 | Коли Фармасьютикал Гмбх | Иммуностимулирующая нуклеиновая кислота с улучшенной иммуностимулирующей эффективностью |
US20050239102A1 (en) | 2003-10-31 | 2005-10-27 | Verdine Gregory L | Nucleic acid binding oligonucleotides |
US7846436B2 (en) | 2003-11-28 | 2010-12-07 | Chemgenes Corporation | Oligonucleotides and related compounds |
AU2003300239A1 (en) | 2003-12-29 | 2005-07-21 | Galapagos Genomics N.V. | Modulators of bone homeostasis identified in a high-throughput screen |
WO2005070859A1 (ja) | 2004-01-27 | 2005-08-04 | Takeshi Wada | フルオラス担体およびそれを用いたオリゴヌクレオチド誘導体の製造方法 |
US20050176045A1 (en) | 2004-02-06 | 2005-08-11 | Dharmacon, Inc. | SNP discriminatory siRNA |
EP1725250A2 (en) | 2004-02-18 | 2006-11-29 | Frutarom Ltd. | Method for the preparation of peptide-oligonucleotide conjugates |
JP3976742B2 (ja) | 2004-02-27 | 2007-09-19 | 江守商事株式会社 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
WO2005085272A1 (ja) | 2004-03-05 | 2005-09-15 | Takeshi Wada | ボラノホスフェートモノマーおよびそれを用いたオリゴヌクレオチド誘導体の製造方法 |
JP4865544B2 (ja) | 2004-03-25 | 2012-02-01 | 株式会社キラルジェン | 立体規則性の高いリボヌクレオチド類縁体及びデオキシリボヌクレオチド類縁体の製造法 |
US20050244869A1 (en) | 2004-04-05 | 2005-11-03 | Brown-Driver Vickie L | Modulation of transthyretin expression |
CA2561741C (en) | 2004-04-05 | 2016-09-27 | Alnylam Pharmaceuticals, Inc. | Processes and reagents for oligonucleotide synthesis and purification |
TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
AU2005248410B2 (en) | 2004-05-27 | 2010-04-22 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Differential expression of molecules associated with acute stroke |
US7759318B1 (en) | 2004-05-28 | 2010-07-20 | Isis Pharmaceuticals, Inc. | Identification of novel pathways, genes and promoter motifs regulating adipogenesis |
WO2005121372A2 (en) | 2004-06-03 | 2005-12-22 | Isis Pharmaceuticals, Inc. | Double strand compositions comprising differentially modified strands for use in gene modulation |
USRE47769E1 (en) | 2004-06-28 | 2019-12-17 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
DK1786472T3 (da) | 2004-08-10 | 2013-04-15 | Genzyme Corp | Antisense-modulering af apolipoprotein B-ekspression |
BRPI0514644A (pt) | 2004-08-26 | 2008-06-17 | Nippon Shinyaku Co Ltd | composto fosforamidita, composto ácido ribonucléico, e método para produzir oligo-rna |
WO2006029258A2 (en) | 2004-09-07 | 2006-03-16 | Archemix Corp. | Aptamer medicinal chemistry |
US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
US20090203132A1 (en) | 2004-09-09 | 2009-08-13 | Swayze Eric E | Pyrrolidinyl groups for attaching conjugates to oligomeric compounds |
CA2580504C (en) | 2004-09-17 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Enhanced antisense oligonucleotides |
EP1807093A2 (en) | 2004-10-13 | 2007-07-18 | Isis Pharmaceuticals, Inc. | Antisense modulation of ptp1b expression |
US7622451B2 (en) | 2004-11-03 | 2009-11-24 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
US8212011B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues |
WO2010096650A1 (en) | 2009-02-20 | 2010-08-26 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
US9120774B2 (en) | 2004-11-03 | 2015-09-01 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
US8212012B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
WO2006050501A2 (en) | 2004-11-03 | 2006-05-11 | University Of Kansas | Novobiocin analogues as anticancer agents |
KR100721928B1 (ko) | 2004-11-05 | 2007-05-28 | 주식회사 바이오씨에스 | CpG 올리고데옥시뉴클레오티드를 함유하는 피부질환의치료 또는 예방용 약학적 조성물 |
EP1657307A1 (en) | 2004-11-16 | 2006-05-17 | Immunotech S.A. | Oligonucleotides that induce the secretion of GM-CSF |
EP1819365B1 (en) | 2004-12-09 | 2014-07-02 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering RNAs |
US9809824B2 (en) | 2004-12-13 | 2017-11-07 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods |
WO2006066260A2 (en) | 2004-12-17 | 2006-06-22 | Thiosense, Inc. | Compositions of and methods for producing phosphorus-chiral monomers and oligomers |
US20070099851A1 (en) | 2004-12-30 | 2007-05-03 | Linn Gregory S | Stable analogues of ribose-1-phosphate and methods for treating diabetes and other metabolic disorders |
US20060183763A1 (en) | 2004-12-31 | 2006-08-17 | Pfizer Inc | Novel pyrrolidyl derivatives of heteroaromatic compounds |
JP4836145B2 (ja) | 2005-01-28 | 2011-12-14 | クウォン,ヒュン−ジョ | マイコバクテリアに由来する、免疫機能刺激用、免疫疾患治療用、アトピー性皮膚炎治療用および/または正常免疫細胞保護用オリゴヌクレオチド |
JP2008531018A (ja) | 2005-02-24 | 2008-08-14 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 免疫刺激性オリゴヌクレオチド |
EP1866319B1 (en) | 2005-04-01 | 2011-11-23 | The Regents of The University of California | Phosphono-pent-2-en-1-yl nucleosides and analogs |
DK1877070T3 (da) | 2005-05-05 | 2009-03-02 | Antisense Pharma Gmbh | Terapeutisk anvendelse af TGF-beta2 antisense-oligonucleotider |
EP1885854B1 (en) | 2005-05-06 | 2012-10-17 | Medtronic, Inc. | Methods and sequences to suppress primate huntington gene expression |
US7902352B2 (en) | 2005-05-06 | 2011-03-08 | Medtronic, Inc. | Isolated nucleic acid duplex for reducing huntington gene expression |
EP3470072A1 (en) | 2005-06-23 | 2019-04-17 | Biogen MA Inc. | Compositions and methods for modulation of smn2 splicing |
US9133517B2 (en) | 2005-06-28 | 2015-09-15 | Medtronics, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin |
EP2062980B1 (en) | 2005-06-28 | 2011-08-31 | Medtronic, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin gene. |
WO2007005941A2 (en) | 2005-07-05 | 2007-01-11 | President And Fellows Of Harvard College | Liver targeted conjugates |
JP4984634B2 (ja) | 2005-07-21 | 2012-07-25 | ソニー株式会社 | 物理情報取得方法および物理情報取得装置 |
ZA200801859B (en) | 2005-07-28 | 2009-07-29 | Id Fish Technology Inc | Method for improving cell permeability to foreign particles |
CA2620856C (en) | 2005-08-29 | 2017-11-28 | Isis Pharmaceuticals, Inc. | Methods for use in modulating mir-122a |
WO2007028065A2 (en) | 2005-08-30 | 2007-03-08 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
US7700567B2 (en) | 2005-09-29 | 2010-04-20 | Supergen, Inc. | Oligonucleotide analogues incorporating 5-aza-cytosine therein |
US20070077993A1 (en) | 2005-09-30 | 2007-04-05 | Midgley Timothy M | Method and apparatus for collecting user game play data and crediting users in a gaming environment |
WO2007047396A2 (en) | 2005-10-12 | 2007-04-26 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
US9308252B2 (en) | 2005-10-27 | 2016-04-12 | Cook Biotech, Inc. | Extracellular matrix materials as vaccine adjuvants for diseases associated with infectious pathogens or toxins |
JP5111385B2 (ja) | 2005-10-28 | 2013-01-09 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | ハンチンチン遺伝子の発現を抑制するための組成物および方法 |
EP1942185A4 (en) | 2005-10-28 | 2009-11-25 | Tosoh Corp | PROCESS FOR PREPARING CAROTINOIDY SYNTHETIZING MICROORGANISM AND METHOD FOR CAROTINOID PRODUCTION |
WO2007059041A2 (en) | 2005-11-11 | 2007-05-24 | Pfizer, Inc. | Combinations and methods of using an immunomodulatory oligodeoxynucleotide |
WO2007064291A1 (en) | 2005-11-30 | 2007-06-07 | Jyoti Chattopadhyaya | Method and compounds for rna synthesis |
EP1957507B1 (en) | 2005-12-02 | 2018-10-24 | Ionis Pharmaceuticals, Inc. | Antibacterial 4,5-substituted aminoglycoside analogs having multiple substituents |
US8076303B2 (en) | 2005-12-13 | 2011-12-13 | Spring Bank Pharmaceuticals, Inc. | Nucleotide and oligonucleotide prodrugs |
PT1979356E (pt) | 2005-12-21 | 2013-11-21 | Pfizer Prod Inc | Carbonilaminopirrolopirazolos, inibidores potentes de cinase |
PL2161038T3 (pl) | 2006-01-26 | 2014-06-30 | Ionis Pharmaceuticals Inc | Kompozycje i ich zastosowanie ukierunkowane na huntingtynę |
CA2640171C (en) | 2006-01-27 | 2014-10-28 | Isis Pharmaceuticals, Inc. | 6-modified bicyclic nucleic acid analogs |
EP1991678B2 (en) | 2006-02-15 | 2020-07-15 | Rechtsanwalt Thomas Beck | Compositions and methods for oligonucleotide formulations |
US7759470B2 (en) | 2006-02-20 | 2010-07-20 | Roche Diagnostics Operations, Inc. | Labeling reagent |
US8383660B2 (en) | 2006-03-10 | 2013-02-26 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
CA2647827A1 (en) | 2006-03-31 | 2007-10-11 | Applied Biosystems Inc. | Reagents useful for synthesizing rhodamine-labeled oligonucleotides |
WO2007118222A2 (en) | 2006-04-06 | 2007-10-18 | Ibis Biosciences, INC | Compositions for the use in identification of fungi |
BRPI0710512A2 (pt) | 2006-04-20 | 2012-06-05 | Hoffmann La Roche | moduladores derivados de diazepan de receptores de quimiocinas |
US8206923B2 (en) | 2006-04-24 | 2012-06-26 | Elvira Garza Gonzalez | Method for detection and multiple, simultaneous quantification of pathogens by means of real-time polymerase chain reaction |
US20100008937A1 (en) | 2006-04-25 | 2010-01-14 | Immune Disease Institute, Inc. | Targeted delivery to leukocytes using non-protein carriers |
GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
AU2007258117B2 (en) | 2006-05-05 | 2013-05-30 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating gene expression |
US8158598B2 (en) | 2006-05-05 | 2012-04-17 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to PTPR alpha |
US20090012120A1 (en) | 2006-05-10 | 2009-01-08 | Board Of Trustees Of Michigan State University | Synthesis of N-heterocycles, beta-amino acids, and allyl amines via aza-payne mediated reaction of ylides and hydroxy aziridines |
DK2066684T3 (da) | 2006-05-11 | 2012-10-22 | Isis Pharmaceuticals Inc | 5´-Modificerede bicycliske nukleinsyreanaloge |
US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
WO2007139190A1 (ja) | 2006-05-31 | 2007-12-06 | Toray Industries, Inc. | 免疫刺激オリゴヌクレオチド及びその医薬用途 |
US8097596B2 (en) | 2006-06-30 | 2012-01-17 | Lakewood-Amedex, Inc. | Compositions and methods for the treatment of muscle wasting |
CA2659103C (en) | 2006-07-12 | 2019-05-21 | The Regents Of The University Of California | Transducible delivery of nucleic acids by reversible phosphotriester charge neutralization protecting groups |
EP2051977A2 (en) | 2006-07-20 | 2009-04-29 | Amgen Inc. | SUBSTITUTED AZOLE AROMATIC HETEROCYCLES AS INHIBITORS OF LLbeta-HSD-1 |
GB0614947D0 (en) | 2006-07-27 | 2006-09-06 | Isis Innovation | Epitope reduction therapy |
CA2660052A1 (en) | 2006-08-04 | 2008-02-07 | Isis Pharmaceuticals, Inc. | Compositions and methods for the modulation of jnk proteins |
AT504194B1 (de) | 2006-09-07 | 2008-07-15 | Oesterr Rotes Kreuz | Bakteriennachweis |
US8138330B2 (en) | 2006-09-11 | 2012-03-20 | Sigma-Aldrich Co. Llc | Process for the synthesis of oligonucleotides |
KR101251707B1 (ko) | 2006-09-27 | 2013-04-11 | 콜리 파마슈티칼 게엠베하 | 면역 자극 활성이 증강된 소수성 T 유사체를 함유하는 CpG 올리고뉴클레오티드 유사체 |
ATE540118T1 (de) | 2006-10-18 | 2012-01-15 | Isis Pharmaceuticals Inc | Antisense-verbindungen |
MX2009004290A (es) | 2006-10-23 | 2009-07-27 | Irm Llc | Inhibidores de proteasas de catepsina. |
KR20090058584A (ko) | 2006-10-26 | 2009-06-09 | 콜리 파마슈티칼 게엠베하 | 올리고리보뉴클레오티드 및 그의 용도 |
FR2908414B1 (fr) | 2006-11-13 | 2012-01-20 | Centre Nat Rech Scient | Immobilisation de proteines membranaires sur un support par l'intermediaire d'une molecule amphiphile |
CA2669917A1 (en) | 2006-11-17 | 2008-05-22 | Dawn M. George | Aminopyrrolidines as chemokine receptor antagonists |
JP2010510807A (ja) | 2006-11-27 | 2010-04-08 | アイシス ファーマシューティカルズ, インコーポレーテッド | 高コレステロール血症を治療するための方法 |
US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
WO2008073959A2 (en) | 2006-12-12 | 2008-06-19 | Idera Pharmaceuticals, Inc. | Synthetic agonists of tlr9 |
UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
EP2125852B1 (en) | 2007-02-15 | 2016-04-06 | Ionis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
RU2559536C2 (ru) | 2007-03-24 | 2015-08-10 | Джензим Корпорейшн | Введение антисмысловых олигонуклеотидов, комплементарных человеческому аполипопротеину в |
US7960353B2 (en) | 2007-05-10 | 2011-06-14 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
JP5646320B2 (ja) | 2007-05-11 | 2014-12-24 | アダイニクス, インコーポレイテッド | 遺伝子発現と疼痛 |
US8222407B2 (en) * | 2007-05-24 | 2012-07-17 | Kyorin Pharmaceutical Co., Ltd. | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in substituent at 14-position |
GB0710186D0 (en) | 2007-05-29 | 2007-07-04 | Texas Instr Denmark | PWM loop with minimum allasing error property |
EP2170917B1 (en) | 2007-05-30 | 2012-06-27 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
BRPI0812740A2 (pt) | 2007-06-05 | 2016-07-19 | Nsab Af Neurosearch Sweden Ab | composto, composição farmacêutica, uso do composto, e, método para tratamento, prevenção ou alívio de um distúrbio do sistema nervoso central de um corpo de animal vivo. |
EP2173760B2 (en) | 2007-06-08 | 2015-11-04 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
EP2164865A2 (en) | 2007-06-13 | 2010-03-24 | Hochschule Mannheim | Compounds for the modulation of huntingtin aggregation, methods and means for identifying such compounds |
ATE462787T1 (de) | 2007-06-18 | 2010-04-15 | Commissariat Energie Atomique | Reversibles sirna-silencing eines mutierten und endogenen huntington-wildtypgens und dessen anwendung zur behandlung von morbus huntington |
GB0712494D0 (en) | 2007-06-27 | 2007-08-08 | Isis Innovation | Substrate reduction therapy |
CA2692579C (en) | 2007-07-05 | 2016-05-03 | Isis Pharmaceuticals, Inc. | 6-disubstituted bicyclic nucleic acid analogs |
JP5737937B2 (ja) | 2007-07-09 | 2015-06-17 | イデラ ファーマシューティカルズ インコーポレイテッドIdera Pharmaceuticals, Inc. | 安定化免疫調節rna(simra)化合物 |
TWI413530B (zh) | 2007-07-20 | 2013-11-01 | Kao Corp | 有機聚矽氧 |
US8008011B2 (en) | 2007-07-31 | 2011-08-30 | University Of Saskatchewan | Genetic variation in pro-melanin-concentrating hormone gene affects carcass traits in cattle |
US7812003B2 (en) | 2007-08-02 | 2010-10-12 | Safe Stephen H | Antisense microRNA and uses therefor |
AU2008286735A1 (en) | 2007-08-15 | 2009-02-19 | Idera Pharmaceuticals, Inc. | Toll like receptor modulators |
CA2701128A1 (en) | 2007-10-01 | 2009-04-09 | Isis Pharmaceuticals, Inc. | Antisense modulation of fibroblast growth factor receptor 4 expression |
KR100886139B1 (ko) | 2007-11-13 | 2009-02-27 | 주식회사 삼천리제약 | 올리고뉴클레오타이드의 제조방법 |
AR069869A1 (es) | 2007-12-21 | 2010-02-24 | Exelixis Inc | Derivados de benzofuro[3,2-d]pirimidinas inhibidores de proteinquinasas,composiciones farmaceuticas que los comprenden y usos de los mismos en el tratamiento del cancer. |
TWI340765B (en) | 2007-12-26 | 2011-04-21 | Ind Tech Res Inst | Oligonucleotide sequences and dna chip for identifying filamentous microorganisms and the identification method thereof |
WO2009089689A1 (en) | 2008-01-15 | 2009-07-23 | Mediatek Inc. | Multimedia presenting system, multimedia processing apparatus thereof, and method for presenting video and audio signals |
WO2009089659A1 (en) | 2008-01-18 | 2009-07-23 | Shanghai Targetdrug Co., Ltd. | Pyrollidine-based compounds |
CA2711587A1 (en) | 2008-02-04 | 2009-08-13 | Galapagos Nv | Target sequences and methods to identify the same, useful in treatment of neurodegenerative diseases |
JP2009190983A (ja) | 2008-02-12 | 2009-08-27 | Tokyo Institute Of Technology | オリゴヌクレオチド誘導体 |
WO2009117589A1 (en) | 2008-03-21 | 2009-09-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising tricyclic nucleosides and methods for their use |
US20110130440A1 (en) | 2008-03-26 | 2011-06-02 | Alnylam Pharmaceuticals, Inc. | Non-natural ribonucleotides, and methods of use thereof |
CN102123716B (zh) | 2008-04-03 | 2013-09-18 | 春堤公司 | 用于治疗病毒感染的化合物和方法 |
US8350022B2 (en) | 2008-04-04 | 2013-01-08 | Universitaet Hamburg | Method for the stereoselective synthesis of phosphorus compounds |
WO2009124238A1 (en) | 2008-04-04 | 2009-10-08 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides |
CA2726866A1 (en) | 2008-05-09 | 2009-11-12 | The University Of British Columbia | Methods and compositions for the treatment of huntington's disease |
US8679750B2 (en) | 2008-05-09 | 2014-03-25 | The University Of British Columbia | Methods and compositions for the treatment of Huntington'S disease |
WO2009140626A2 (en) | 2008-05-15 | 2009-11-19 | Dynavax Technologies Corporation | Long term disease modification using immunostimulatory oligonucleotides |
WO2009143390A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc. | Methods for modulating expression of rbp4 |
WO2009143391A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc | Methods for modulation expression of creb |
WO2009143387A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc. | Modulation of smrt expression |
WO2009148605A2 (en) | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
AU2009266806A1 (en) | 2008-07-03 | 2010-01-07 | Exelixis Inc. | CDK modulators |
US8410070B2 (en) | 2008-09-12 | 2013-04-02 | University Of Louisville Research Foundation, Inc. | Compositions and methods for treating cancer, inhibiting proliferation, and inducing cell death |
WO2010030858A1 (en) | 2008-09-15 | 2010-03-18 | Enanta Pharmaceuticals, Inc. | 4'-allene-substituted nucleoside derivatives |
EP3067359A1 (en) | 2008-09-23 | 2016-09-14 | Scott G. Petersen | Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating rna interference |
US8501805B2 (en) | 2008-09-24 | 2013-08-06 | Isis Pharmaceuticals, Inc. | Substituted alpha-L-bicyclic nucleosides |
DK2361256T3 (da) | 2008-09-24 | 2013-07-01 | Isis Pharmaceuticals Inc | Cyclohexenyl-nukleinsyreanaloger |
AU2009302385B2 (en) | 2008-10-07 | 2015-12-03 | President And Fellows Of Harvard College | Telomerase inhibitors and methods of use thereof |
CN104857526B (zh) | 2008-10-22 | 2019-03-05 | 夸克制药公司 | 治疗眼部疾病的方法 |
CN102264374B (zh) | 2008-10-24 | 2015-01-07 | Isis制药公司 | 5′和2′双取代的核苷和由其制备的低聚化合物 |
EP2358398A2 (en) | 2008-10-24 | 2011-08-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
WO2010072831A1 (en) | 2008-12-23 | 2010-07-01 | Girindus America, Inc | Sulfurizing reagents and their use for oligonucleotides synthesis |
WO2010080953A1 (en) | 2009-01-08 | 2010-07-15 | Isis Pharmaceuticals, Inc. | Transgenic murine model of human lipoprotein metabolism, hypercholesterolemia and cardiovascular disease |
KR20100087540A (ko) | 2009-01-28 | 2010-08-05 | 삼성전자주식회사 | 잉크젯 기록용 잉크 조성물 |
WO2010091301A1 (en) | 2009-02-06 | 2010-08-12 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and excipients |
EP2396409A2 (en) | 2009-02-10 | 2011-12-21 | Idera Pharmaceuticals, Inc. | Synthetic rna-based agonists of tlr7 |
US8975389B2 (en) | 2009-03-02 | 2015-03-10 | Alnylam Pharmaceuticals, Inc. | Nucleic acid chemical modifications |
US9107933B2 (en) | 2009-03-16 | 2015-08-18 | Isis Pharmaceuticals, Inc. | Compositions and methods of targeting apolipoprotein B for the reduction of apolipoprotein C-III |
WO2010113937A1 (ja) | 2009-03-31 | 2010-10-07 | 武田薬品工業株式会社 | ヌクレオシドの製造方法 |
US8987222B2 (en) | 2009-04-08 | 2015-03-24 | University Of Massachusetts | Single nucleotide polymorphism (SNP) targeting therapies for the treatment of huntington'S disease |
CA2759098A1 (en) | 2009-04-14 | 2010-10-21 | Smith Holdings, Llc | Methods and compositions for the treatment of medical conditions involving cellular programming |
US9260493B2 (en) | 2009-05-07 | 2016-02-16 | The Regents Of The University Of California | Transducible delivery of nucleic acids using modified dsRNA binding domains |
AU2010256836A1 (en) | 2009-06-01 | 2012-01-19 | The Regents Of The University Of California | Nucleic acid delivery compositions and methods of use thereof |
TWI494125B (zh) | 2009-06-05 | 2015-08-01 | Infectious Disease Res Inst | 合成的葡萄吡喃糖基脂質佐劑 |
CN116440150A (zh) | 2009-06-17 | 2023-07-18 | 冷泉港实验室 | 用于在对象中调节smn2剪接的组合物和方法 |
JP5670097B2 (ja) | 2009-06-19 | 2015-02-18 | 花王株式会社 | 二層分離型毛髪化粧料 |
WO2010150789A1 (ja) | 2009-06-23 | 2010-12-29 | 武田薬品工業株式会社 | 核酸の合成法 |
US8329024B2 (en) | 2009-07-06 | 2012-12-11 | Ada Technologies, Inc. | Electrochemical device and method for long-term measurement of hypohalites |
WO2011005860A2 (en) | 2009-07-07 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | 5' phosphate mimics |
EP2451974A2 (en) | 2009-07-08 | 2012-05-16 | Idera Pharmaceuticals, Inc. | Oligonucleotide-based compounds as inhibitors of toll-like receptors |
WO2011010706A1 (ja) | 2009-07-23 | 2011-01-27 | 武田薬品工業株式会社 | Fgf21シスエレメント結合物質 |
WO2011015572A1 (en) | 2009-08-03 | 2011-02-10 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
WO2011015573A1 (en) | 2009-08-03 | 2011-02-10 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
UA107360C2 (en) | 2009-08-05 | 2014-12-25 | Biogen Idec Inc | Bicyclic aryl sphingosine 1-phosphate analogs |
WO2011017521A2 (en) | 2009-08-06 | 2011-02-10 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
US8927553B2 (en) | 2009-08-10 | 2015-01-06 | Daljit Singh Dhanoa | Deuterium-enriched alkyl sulfonamides and uses thereof |
NZ714887A (en) | 2009-09-11 | 2019-07-26 | Ionis Pharmaceuticals Inc | Modulation of huntingtin expression |
CN102574888A (zh) | 2009-09-16 | 2012-07-11 | 株式会社启拉坚 | 用于rna及其衍生物的合成的新型保护基 |
EP2480667A4 (en) | 2009-09-25 | 2013-07-03 | Isis Pharmaceuticals Inc | MODULATION OF TTC39 EXPRESSION FOR HDL INCREASE |
JP5629324B2 (ja) | 2009-10-15 | 2014-11-19 | ファイザー・インク | ピロロ[2,3−d]ピリミジン化合物 |
TWI475051B (zh) | 2009-11-18 | 2015-03-01 | Kao Corp | Organic polysiloxane |
JP5809408B2 (ja) | 2009-11-25 | 2015-11-10 | 花王株式会社 | 毛髪化粧料 |
WO2011075560A1 (en) | 2009-12-17 | 2011-06-23 | Merck Sharp & Dohme Corp. | Aminopyrimidines as syk inhibitors |
JP2013515953A (ja) | 2009-12-28 | 2013-05-09 | アチラ ラボズ プライベート リミテッド | 診断用ゲル組成物、前記診断用ゲル組成物の製造方法 |
JP5822845B2 (ja) | 2010-01-08 | 2015-11-25 | アイシス ファーマシューティカルズ, インコーポレーテッド | アンジオポエチン様3発現の調節 |
US8750507B2 (en) | 2010-01-25 | 2014-06-10 | Cisco Technology, Inc. | Dynamic group creation for managed key servers |
WO2011097643A1 (en) | 2010-02-08 | 2011-08-11 | Isis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
US9006198B2 (en) | 2010-02-08 | 2015-04-14 | Isis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
JP5922587B2 (ja) | 2010-02-10 | 2016-05-24 | グラクソスミスクライン エルエルシー | 6−アミノ−2−{[(1s)−1−メチルブチル]オキシ}−9−[5−(1−ピペリジニル)ペンチル]−7,9−ジヒドロ−8h−プリン−8−オンマレイン酸塩 |
WO2011108682A1 (ja) | 2010-03-05 | 2011-09-09 | 国立大学法人 東京大学 | リボヌクレオシドホスホロチオエートの製造方法 |
WO2011127175A1 (en) | 2010-04-06 | 2011-10-13 | Isis Pharmaceuticals, Inc. | Modulation of cd130 (gp130) expression |
WO2011127307A1 (en) | 2010-04-07 | 2011-10-13 | Isis Pharmaceuticals, Inc. | Modulation of cetp expression |
WO2011133871A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | 5'-end derivatives |
US9127033B2 (en) | 2010-04-28 | 2015-09-08 | Isis Pharmaceuticals, Inc. | 5′ modified nucleosides and oligomeric compounds prepared therefrom |
JP6005628B2 (ja) | 2010-04-28 | 2016-10-12 | アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. | 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物 |
WO2011139911A2 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
WO2011135396A1 (en) | 2010-04-30 | 2011-11-03 | Cellectis | Method for modulating double-strand break-induced homologous recombination |
GB201008902D0 (en) | 2010-05-27 | 2010-07-14 | Imp Innovations Ltd | Membrane enhanced polymer sythesis |
CN103221549A (zh) | 2010-08-31 | 2013-07-24 | 默沙东公司 | 用于递送寡核苷酸的新型简单化学实体和方法 |
US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
WO2012043633A1 (ja) | 2010-09-30 | 2012-04-05 | 独立行政法人国立精神・神経医療研究センター | 優性変異遺伝子発現抑制剤 |
KR101381048B1 (ko) | 2010-10-20 | 2014-04-14 | 씨제이제일제당 (주) | O-포스포세린 생산 균주 및 이로부터 생산된 o-포스포세린으로부터 l-시스테인 또는 이의 유도체의 생산방법 |
WO2012058210A1 (en) | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA) |
DK2638163T3 (en) | 2010-11-12 | 2017-07-24 | Massachusetts Gen Hospital | POLYCOMB-ASSOCIATED NON-CODING RNAs |
WO2012073857A1 (ja) | 2010-11-30 | 2012-06-07 | 株式会社キラルジェン | 2'-o-修飾rna |
WO2012092367A1 (en) | 2010-12-28 | 2012-07-05 | University Of Rochester | Nucleic acid binding compounds, methods of making, and use thereof |
EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
CA2827380C (en) | 2011-02-12 | 2020-08-25 | University Of Iowa Research Foundation | Therapeutic nucleic acids |
WO2012151324A1 (en) | 2011-05-02 | 2012-11-08 | Isis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with usher syndrome |
FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
DK2734208T3 (en) | 2011-07-19 | 2017-06-19 | Wave Life Sciences Ltd | PROCEDURES FOR SYNTHESIS OF FUNCTIONALIZED NUCLEIC ACIDS |
AR088140A1 (es) | 2011-07-19 | 2014-05-14 | Univ Idaho | Sonda y metodo para direccionar acidos nucleicos |
US20140303235A1 (en) | 2011-08-11 | 2014-10-09 | Isis Pharmaceuticals, Inc. | Linkage modified gapped oligomeric compounds and uses thereof |
EP2751269B1 (en) | 2011-08-29 | 2016-03-23 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
US20140080896A1 (en) | 2011-08-30 | 2014-03-20 | The Regents Of The University Of California | Identification of small molecules that facilitate therapeutic exon skipping |
CA2846307C (en) | 2011-08-31 | 2020-03-10 | Hospital District Of Helsinki And Uusimaa | Method for diagnosing a neurodegenerative disease |
WO2013036833A1 (en) | 2011-09-09 | 2013-03-14 | Mayo Foundation For Medical Education And Research | Detecting frontotemporal dementia and amyotrophic lateral sclerosis |
JP6317675B2 (ja) | 2011-11-30 | 2018-04-25 | サレプタ セラピューティクス, インコーポレイテッド | 延長リピート病を処置するためのオリゴヌクレオチド |
US10557136B2 (en) | 2011-12-12 | 2020-02-11 | Oncolmmunin Inc. | In vivo delivery of oligonucleotides |
EP2791335B1 (en) | 2011-12-16 | 2018-11-14 | National University Corporation Tokyo Medical and Dental University | Chimeric double-stranded nucleic acid |
CN102675386B (zh) | 2011-12-24 | 2014-07-02 | 河南科技大学 | 一种龙胆苦苷分离提纯方法 |
US8957042B2 (en) | 2012-03-07 | 2015-02-17 | The Texas A&M University System | Cancer treatment targeting non-coding RNA overexpression |
EP2834258B1 (en) | 2012-03-13 | 2017-01-04 | Gilead Sciences, Inc. | 2'- substituted carba-nucleoside analogs for antiviral treatment |
US9809616B2 (en) | 2012-10-29 | 2017-11-07 | Emory University | Pyrimidine nucleosides and their monophosphate prodrugs for the treatment of viral infections and cancer |
KR20130114435A (ko) | 2012-04-09 | 2013-10-17 | 삼성전자주식회사 | 다수의 전극을 갖는 생분자 검출 장치 |
EP2841578B1 (en) | 2012-04-23 | 2017-06-07 | BioMarin Technologies B.V. | RNA modulating oligonucleotides with improved characteristics for the treatment of neuromuscular disorders |
SG11201407674TA (en) | 2012-05-22 | 2014-12-30 | Idenix Pharmaceuticals Inc | D-amino acid compounds for liver disease |
IN2014DN10144A (ja) | 2012-05-30 | 2015-08-21 | Hokkaido System Science Co Ltd | |
JP6246121B2 (ja) | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | キラル核酸アジュバント |
SG11201500232UA (en) | 2012-07-13 | 2015-04-29 | Wave Life Sciences Pte Ltd | Chiral control |
US9598458B2 (en) | 2012-07-13 | 2017-03-21 | Wave Life Sciences Japan, Inc. | Asymmetric auxiliary group |
JP2015525797A (ja) | 2012-08-06 | 2015-09-07 | アルニラム・ファーマシューティカルズ・インコーポレーテッド | 糖質コンジュゲートrna剤およびその調製方法 |
US9403865B2 (en) | 2012-08-15 | 2016-08-02 | Ionis Pharmaceuticals, Inc. | Method of preparing oligomeric compounds using modified capping protocols |
EP4086347A3 (en) | 2012-10-12 | 2023-01-11 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
EP2906258A4 (en) | 2012-10-15 | 2016-08-10 | Ionis Pharmaceuticals Inc | COMPOSITIONS FOR MODULATING THE EXPRESSION OF C90RF72 |
FI2906696T4 (fi) | 2012-10-15 | 2023-03-18 | Menetelmiä c9orf72:n ilmentymisen moduloimiseksi | |
EP2906697A4 (en) | 2012-10-15 | 2016-06-22 | Ionis Pharmaceuticals Inc | METHODS OF MONITORING C9ORF72 EXPRESSION |
EP2725029A1 (en) | 2012-10-29 | 2014-04-30 | Laboratoire Biodim | New antibacterial compounds and biological applications thereof |
WO2014069520A1 (ja) | 2012-10-31 | 2014-05-08 | 武田薬品工業株式会社 | 新規修飾核酸 |
CN104884618A (zh) | 2012-11-15 | 2015-09-02 | 罗氏创新中心哥本哈根有限公司 | 寡核苷酸缀合物 |
RU2015120645A (ru) | 2012-11-26 | 2017-01-10 | Рош Инновейшен Сентер Копенгаген А/С | Композиции и способы модуляции экспрессии рецептора фактора роста фибробластов 3 типа (fgfr3) |
WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
CA2893801A1 (en) | 2013-01-30 | 2014-08-07 | F. Hoffmann-La Roche Ag | Lna oligonucleotide carbohydrate conjugates |
EP3778618A1 (en) | 2013-02-04 | 2021-02-17 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
CA2900238A1 (en) | 2013-02-22 | 2014-08-28 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) molecules containing a 2' internucleoside linkage |
CA2901983A1 (en) | 2013-03-01 | 2014-09-04 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
US20160050930A1 (en) | 2013-03-28 | 2016-02-25 | Syngenta Limited | Methods of controlling neonicotinoid resistant pests |
EP2978317A1 (en) | 2013-03-28 | 2016-02-03 | Syngenta Participations AG | Methods of controlling neonicotinoid resistant pests |
PT2992098T (pt) | 2013-05-01 | 2019-07-05 | Ionis Pharmaceuticals Inc | Composições e métodos para modular a expressão de hbv e ttr |
MX363846B (es) | 2013-05-24 | 2019-04-05 | Roche Innovation Ct Copenhagen As | Moduladores de oligonucleotido de linfoma linfocitico cronico/linfoma de celulas b 11a (bcl11a) y sus usos. |
EP3015467A4 (en) | 2013-05-24 | 2016-11-02 | Ajinomoto Kk | PROCESS FOR THE PRODUCTION OF MORPHOLINO-OLIGONUCLEOTIDE |
EP3004347B1 (en) | 2013-05-30 | 2018-09-26 | National University Corporation Tokyo Medical and Dental University | Double-stranded agents for delivering therapeutic oligonucleotides |
CN105324119A (zh) | 2013-06-16 | 2016-02-10 | 国立大学法人东京医科齿科大学 | 具有外显子跳跃效应的双链反义核酸 |
US20160122761A1 (en) | 2013-06-21 | 2016-05-05 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
LT3013959T (lt) | 2013-06-27 | 2020-03-10 | Roche Innovation Center Copenhagen A/S | Priešprasmiai oligomerai ir konjugatai, nukreirti į pcsk9 |
TWI772856B (zh) | 2013-07-19 | 2022-08-01 | 美商百健Ma公司 | 用於調節τ蛋白表現之組合物 |
ES2750608T3 (es) | 2013-07-25 | 2020-03-26 | Exicure Inc | Construcciones esféricas a base de ácido nucleico como agentes inmunoestimulantes para uso profiláctico y terapéutico |
WO2015017675A2 (en) | 2013-07-31 | 2015-02-05 | Isis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
BR112016004352A2 (pt) | 2013-09-06 | 2017-09-12 | Syngenta Participations Ag | compostos inseticidas |
US10385088B2 (en) | 2013-10-02 | 2019-08-20 | Modernatx, Inc. | Polynucleotide molecules and uses thereof |
MX2016004249A (es) | 2013-10-03 | 2016-11-08 | Moderna Therapeutics Inc | Polinulcleotidos que codifican el receptor de lipoproteina de baja densidad. |
US9988627B2 (en) | 2013-10-04 | 2018-06-05 | Novartis Ag | Formats for organic compounds for use in RNA interference |
EP4166667A3 (en) | 2013-10-11 | 2023-08-02 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
WO2015057738A1 (en) | 2013-10-14 | 2015-04-23 | Isis Pharmaceuticals, Inc. | Methods for modulating expression of c9orf72 antisense transcript |
WO2015057727A1 (en) | 2013-10-14 | 2015-04-23 | Isis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
KR102431079B1 (ko) | 2013-11-11 | 2022-08-11 | 상가모 테라퓨틱스, 인코포레이티드 | 헌팅턴병을 치료하기 위한 방법 및 조성물 |
CA2928349A1 (en) | 2013-11-14 | 2015-05-21 | Roche Innovation Center Copenhagen A/S | Apob antisense conjugate compounds |
EP3053585A1 (en) | 2013-12-13 | 2016-08-10 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
US10160969B2 (en) | 2014-01-16 | 2018-12-25 | Wave Life Sciences Ltd. | Chiral design |
WO2015143078A1 (en) | 2014-03-18 | 2015-09-24 | University Of Massachusetts | Raav-based compositions and methods for treating amyotrophic lateral sclerosis |
EP3647318B1 (en) | 2014-04-28 | 2021-06-30 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
SI3137605T1 (sl) | 2014-05-01 | 2021-02-26 | Ionis Pharmaceuticals, Inc. | Sestavki in metode za modulacijo ekspresije angiopoetin 3-podobnega |
RU2691102C2 (ru) | 2014-05-08 | 2019-06-11 | Сангамо Байосайенсиз, Инк. | Способы и композиции для лечения болезни хантингтона |
AU2015264263B2 (en) | 2014-05-20 | 2021-08-05 | University Of Iowa Research Foundation | Huntington's disease therapeutic compounds |
US20160017327A1 (en) | 2014-07-11 | 2016-01-21 | The Johns Hopkins University | Phosphorodiamidate morpholino oligomers (pmos) and their use in suppression of mutant huntingtin expression and attenuation of neurotoxicity |
WO2016011226A1 (en) | 2014-07-16 | 2016-01-21 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
EP2982758A1 (en) | 2014-08-04 | 2016-02-10 | Centre Hospitalier Universitaire Vaudois (CHUV) | Genome editing for the treatment of huntington's disease |
WO2016021683A1 (ja) | 2014-08-07 | 2016-02-11 | 武田薬品工業株式会社 | カチオン性脂質 |
WO2016024205A1 (en) | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
WO2016027168A2 (en) | 2014-08-20 | 2016-02-25 | Lifesplice Pharma Llc | Splice modulating oligonucleotides and methods of use thereof |
WO2016037191A1 (en) | 2014-09-05 | 2016-03-10 | Health Research, Inc. | Use of huntingtin-derived plasmids and peptides for active immunization as a huntington's disease (hd) therapeutic |
WO2016081444A1 (en) | 2014-11-17 | 2016-05-26 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof |
EP3220921A1 (en) | 2014-11-19 | 2017-09-27 | Roche Innovation Center Copenhagen A/S | Lna chiral phosphorothioates |
DK3234131T3 (da) | 2014-12-16 | 2020-06-29 | Roche Innovation Ct Copenhagen As | Fremgangsmåde til screening af kiral toksicitet |
CA2971920C (en) | 2014-12-24 | 2024-05-07 | Uniqure Ip B.V. | Rnai induced huntingtin gene suppression |
US9688707B2 (en) | 2014-12-30 | 2017-06-27 | Ionis Pharmaceuticals, Inc. | Bicyclic morpholino compounds and oligomeric compounds prepared therefrom |
WO2016112132A1 (en) | 2015-01-06 | 2016-07-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
MX2017010066A (es) | 2015-02-04 | 2017-11-01 | Hoffmann La Roche | Oligomeros antisentido de tau y usos de los mismos. |
JP6772156B2 (ja) | 2015-02-04 | 2020-10-21 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 治療用分子を選択する方法 |
WO2016127002A1 (en) | 2015-02-04 | 2016-08-11 | Bristol-Myers Squibb Company | Lna oligonucleotides with alternating flanks |
TN2017000354A1 (en) | 2015-02-10 | 2019-01-16 | Genzyme Corp | VARIANT RNAi |
WO2016130806A2 (en) | 2015-02-13 | 2016-08-18 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
EP3262174A4 (en) | 2015-02-23 | 2018-10-17 | Ionis Pharmaceuticals, Inc. | Compounds and methods for increasing antisense activity |
US20180036335A1 (en) | 2015-03-03 | 2018-02-08 | Ionis Pharmaceuticals, Inc. | Compositions for modulating mecp2 expression |
WO2016145142A1 (en) | 2015-03-10 | 2016-09-15 | Emory University | Nucleotide and nucleoside therapeutics compositions and uses related thereto |
WO2016154096A1 (en) | 2015-03-20 | 2016-09-29 | Ionis Pharmaceuticals, Inc. | Modulation of smggds expression |
WO2016161374A1 (en) | 2015-04-03 | 2016-10-06 | University Of Massachusetts | Oligonucleotide compounds for targeting huntingtin mrna |
US10851371B2 (en) | 2015-04-10 | 2020-12-01 | Ionis Pharmaceuticals, Inc. | Modulation of SMN expression |
ES2791995T3 (es) | 2015-04-16 | 2020-11-06 | Ionis Pharmaceuticals Inc | Composiciones para modular la expresión de C90RF72 |
US10407678B2 (en) | 2015-04-16 | 2019-09-10 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
WO2017004261A1 (en) | 2015-06-29 | 2017-01-05 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
US10494632B2 (en) | 2015-07-10 | 2019-12-03 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof |
SG10202006563PA (en) | 2015-07-10 | 2020-08-28 | Ionis Pharmaceuticals Inc | Modulators of diacyglycerol acyltransferase 2 (dgat2) |
CA2989970A1 (en) | 2015-07-17 | 2017-01-26 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
WO2017019660A1 (en) | 2015-07-27 | 2017-02-02 | Alnylam Pharmaceuticals, Inc. | Xanthine dehydrogenase (xdh) irna compositions and methods of use thereof |
CA2994285A1 (en) | 2015-07-31 | 2017-02-09 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated diseases |
DK3341479T3 (da) | 2015-08-24 | 2020-02-24 | Roche Innovation Ct Copenhagen As | LNA-G-Proces |
EA201890571A1 (ru) | 2015-08-25 | 2018-10-31 | Элнилэм Фармасьютикалз, Инк. | Способы и композиции для лечения нарушения, ассоциированного с геном пропротеинконвертазы субтилизин/кексинового типа (pcsk9) |
WO2017040078A1 (en) | 2015-09-02 | 2017-03-09 | Alnylam Pharmaceuticals, Inc. | PROGRAMMED CELL DEATH 1 LIGAND 1 (PD-L1) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
WO2017048620A1 (en) | 2015-09-14 | 2017-03-23 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof |
US10874686B2 (en) | 2015-10-01 | 2020-12-29 | Memorial Sloan-Kettering Cancer Center | Anthranilyl-adenosinemonosulfamate analogs and uses thereof |
CA3000709A1 (en) | 2015-10-01 | 2017-04-06 | Memorial Sloan-Kettering Cancer Center | Inhibitors of menaquinone biosynthesis |
US10577388B2 (en) | 2015-10-02 | 2020-03-03 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugation process |
AU2016334232B2 (en) | 2015-10-09 | 2022-05-26 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods thereof |
WO2017068087A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotide detection method |
EP3394258B1 (en) | 2015-10-22 | 2021-09-22 | Roche Innovation Center Copenhagen A/S | In vitro toxicity screening assay |
WO2017079291A1 (en) | 2015-11-02 | 2017-05-11 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating c90rf72 |
AU2016352836B2 (en) | 2015-11-12 | 2020-06-25 | F. Hoffmann-La Roche Ag | Oligonucleotides for inducing paternal UBE3A expression |
AU2017234150B2 (en) | 2016-03-13 | 2021-09-16 | Wave Life Sciences Ltd. | Compositions and methods for phosphoramidite and oligonucleotide synthesis |
KR102417646B1 (ko) | 2016-03-14 | 2022-07-07 | 에프. 호프만-라 로슈 아게 | Pd-l1 발현의 감소를 위한 올리고뉴클레오티드 |
EP3430021A1 (en) | 2016-03-18 | 2019-01-23 | Roche Innovation Center Copenhagen A/S | Acyl-protected l-lna-guanosine monomers |
WO2017165489A1 (en) | 2016-03-23 | 2017-09-28 | Emory University | Antiviral agents for treating zika and dengue virus infections |
US20190142856A1 (en) | 2016-04-13 | 2019-05-16 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
KR102468177B1 (ko) | 2016-04-14 | 2022-11-16 | 에프. 호프만-라 로슈 아게 | 트리틸-모노-GalNAc 화합물 및 이의 용도 |
MA45290A (fr) | 2016-05-04 | 2019-03-13 | Wave Life Sciences Ltd | Procédés et compositions d'agents biologiquement actifs |
MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
US11261209B2 (en) | 2016-05-12 | 2022-03-01 | Roche Innovation Center Copenhagen A/S | Enhanced coupling of stereodefined oxazaphospholidine phosphoramidite monomers to nucleoside or oligonucleotide |
EP3455354B1 (en) | 2016-05-13 | 2023-07-12 | Roche Diagnostics GmbH | Protein-based sample collection matrices and devices |
EP3458464A1 (en) | 2016-05-18 | 2019-03-27 | ETH Zurich | Stereoselective synthesis of phosphorothioate oligoribonucleotides |
JP2019520339A (ja) | 2016-06-03 | 2019-07-18 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | オリゴヌクレオチド、その組成物および方法 |
EP3473270B1 (en) | 2016-06-20 | 2022-11-30 | Genahead Bio, Inc. | Antibody-drug conjugate |
US20190264267A1 (en) | 2016-07-25 | 2019-08-29 | Wave Life Sciences Ltd. | Phasing |
EP3544987A4 (en) | 2016-11-23 | 2020-11-18 | Wave Life Sciences Ltd. | COMPOSITIONS AND SYNTHESIS OF PHOSPHORAMIDITES AND OLIGONUCLEOTIDES |
-
2012
- 2012-07-13 DK DK12814522.4T patent/DK2734208T3/en active
- 2012-07-13 CN CN201280041560.0A patent/CN103796657B/zh active Active
- 2012-07-13 SG SG10201700554VA patent/SG10201700554VA/en unknown
- 2012-07-13 EP EP12814522.4A patent/EP2734208B1/en active Active
- 2012-07-13 ES ES12814522.4T patent/ES2626488T3/es active Active
- 2012-07-13 WO PCT/US2012/046805 patent/WO2013012758A1/en active Application Filing
- 2012-07-13 BR BR112014001244A patent/BR112014001244A2/pt not_active Application Discontinuation
- 2012-07-13 CA CA2842358A patent/CA2842358C/en active Active
- 2012-07-13 JP JP2014521681A patent/JP6128529B2/ja active Active
- 2012-07-13 US US14/233,579 patent/US9605019B2/en active Active
- 2012-07-13 CN CN201710437875.1A patent/CN107365339A/zh active Pending
- 2012-07-13 AU AU2012284265A patent/AU2012284265B2/en active Active
- 2012-07-13 RU RU2014105311/04A patent/RU2014105311A/ru unknown
- 2012-07-13 KR KR1020147004108A patent/KR20140068884A/ko not_active Application Discontinuation
- 2012-07-13 EP EP17158311.5A patent/EP3248982A1/en not_active Withdrawn
- 2012-07-13 MX MX2014000716A patent/MX347361B/es active IP Right Grant
-
2014
- 2014-01-19 IL IL230522A patent/IL230522B/en active IP Right Grant
- 2014-11-26 HK HK14111931.3A patent/HK1198479A1/xx unknown
-
2016
- 2016-07-28 US US15/222,910 patent/US20170029457A1/en not_active Abandoned
-
2017
- 2017-04-04 JP JP2017074528A patent/JP6490133B2/ja active Active
-
2018
- 2018-03-30 US US15/941,494 patent/US10280192B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3484473A (en) * | 1967-05-12 | 1969-12-16 | Buckman Labor Inc | Methylene bisesters of thiolsulfonic acids |
JP2002533087A (ja) * | 1998-12-21 | 2002-10-08 | ジェネンカー インターナショナル,インコーポレイティド | 複数荷電変種を有する化学修飾酵素 |
WO2011005761A1 (en) * | 2009-07-06 | 2011-01-13 | Ontorii, Inc | Novel nucleic acid prodrugs and methods use thereof |
Non-Patent Citations (4)
Title |
---|
APPLIED SPECTROSCOPY, vol. 20, no. 2, JPN6016031703, 1966, pages 73 - 79, ISSN: 0003899308 * |
CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 12, no. 11, JPN6016031705, 1964, pages 1271 - 1276, ISSN: 0003899309 * |
JOURNAL OF MEDICINAL CHEMISTRY, vol. 7, no. 5, JPN6016031701, 1964, pages 671 - 673, ISSN: 0003899307 * |
TETRAHEDRON LETTERS, vol. 36, no. 5, JPN6016031699, 1995, pages 703 - 706, ISSN: 0003899306 * |
Also Published As
Publication number | Publication date |
---|---|
CN103796657A (zh) | 2014-05-14 |
US9605019B2 (en) | 2017-03-28 |
US20170029457A1 (en) | 2017-02-02 |
EP3248982A1 (en) | 2017-11-29 |
US20140194610A1 (en) | 2014-07-10 |
JP2014522862A (ja) | 2014-09-08 |
CN107365339A (zh) | 2017-11-21 |
ES2626488T3 (es) | 2017-07-25 |
ES2626488T8 (es) | 2017-08-14 |
CN103796657B (zh) | 2017-07-11 |
KR20140068884A (ko) | 2014-06-09 |
JP6490133B2 (ja) | 2019-03-27 |
EP2734208A1 (en) | 2014-05-28 |
MX2014000716A (es) | 2014-05-22 |
US20180222936A1 (en) | 2018-08-09 |
IL230522B (en) | 2018-02-28 |
BR112014001244A2 (pt) | 2017-02-21 |
CA2842358A1 (en) | 2013-01-24 |
US10280192B2 (en) | 2019-05-07 |
EP2734208A4 (en) | 2015-03-18 |
SG10201700554VA (en) | 2017-03-30 |
IL230522A0 (en) | 2014-03-31 |
CA2842358C (en) | 2020-07-14 |
RU2014105311A (ru) | 2015-08-27 |
JP6128529B2 (ja) | 2017-05-17 |
HK1198479A1 (en) | 2015-05-08 |
EP2734208B1 (en) | 2017-03-01 |
AU2012284265A1 (en) | 2014-02-06 |
AU2012284265B2 (en) | 2017-08-17 |
DK2734208T3 (en) | 2017-06-19 |
WO2013012758A1 (en) | 2013-01-24 |
MX347361B (es) | 2017-04-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6490133B2 (ja) | 官能化核酸の合成のための方法 | |
JP6038860B2 (ja) | リン原子修飾核酸の合成方法 | |
JP4865544B2 (ja) | 立体規則性の高いリボヌクレオチド類縁体及びデオキシリボヌクレオチド類縁体の製造法 | |
JP5998326B2 (ja) | 新規核酸プロドラッグおよびその使用方法 | |
JP7263236B2 (ja) | 新規二環式ヌクレオシドおよびそれから調製されたオリゴマー |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180227 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180523 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180718 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180824 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180830 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181023 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190116 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190219 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190226 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6490133 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |